样式: 排序: IF: - GO 导出 标记为已读
-
14-3-3ζ Suppresses RANKL Signaling by Destabilizing TRAF6 J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-21 R. Ayyasamy, S. Fan, P. Czernik, B. Lecka-Czernik, S. Chattopadhyay, R. Chakravarti
Macrophages are essential regulators of inflammation and bone loss. RANKL, a pro-inflammatory cytokine, is responsible for macrophage differentiation to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout () rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However
-
Designing monomeric IFNγ: The significance of domain-swapped dimer structure in IFNγ immune responses J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-13 Yota Goto, Takamitsu Miyafusa, Shinya Honda
Interferon (IFN) γ can initiate immune responses by inducing the expression of major histocompatibility complex molecules, suggesting its potential for cancer immunotherapy. However, it also has an immunosuppressive function that limits its application as a therapeutic agent. IFNγ has a characteristic domain-swapped dimer structure with two of the six α-helices exchanged with each other. As we hypothesized
-
A designed ankyrin-repeat protein that targets Parkinson’s disease-associated LRRK2 J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Verena Dederer, Marta Sanz Murillo, Eva P. Karasmanis, Kathryn S. Hatch, Deep Chatterjee, Franziska Preuss, Kamal R. Abdul Azeez, Landon Vu Nguyen, Christian Galicia, Birgit Dreier, Andreas Plückthun, Wim Versees, Sebastian Mathea, Andres E. Leschziner, Samara L. Reck-Peterson, Stefan Knapp
Leucine rich repeat kinase 2 (LRRK2) is a large multidomain protein containing two catalytic domains, a kinase and a GTPase, as well as protein interactions domains, including a WD40 domain. The association of increased LRRK2 kinase activity with both the familial and sporadic forms of Parkinson’s disease has led to an intense interest in determining its cellular function. However, small molecule probes
-
Structural studies of WDR5 in complex with MBD3C WIN motif reveal a unique binding mode J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Yang Yang, Li Xu, Shuting Zhang, Liangrui Yao, Yuqing Ding, Wenwen Li, Xuemin Chen
The nucleosome remodeling and deacetylase (NuRD) complex plays a pivotal role in chromatin regulation and transcriptional repression. In mice, methyl-CpG binding domain 3 isoform C (MBD3C) interacts specifically with the histone H3 binding protein WD repeat-containing protein 5 (WDR5) and forms the WDR5-MBD3C/Norde complex. Despite the functional significance of this interaction on embryonic stem cell
-
Reconstitution of the alternative pathway of the complement system enables rapid delineation of the mechanism of action of novel inhibitors J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Andrew C. Goodrich, Norbert Leclair, Nita Shillova, William D. Morton, Arthur J. Wittwer, Kelly M. Loyet, Rami N. Hannoush
The complement system plays a critical role in the innate immune response, acting as a first line of defense against invading pathogens. However, dysregulation of the complement system is implicated in the pathogenesis of numerous diseases, ranging from Alzheimer’s to age-related macular degeneration and rare blood disorders. As such, complement inhibitors have enormous potential to alleviate disease
-
Discovery of a class of glycosaminoglycan lyases with ultrabroad substrate spectrum and their substrate structure preferences J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Lin Wei, Ruyi Zou, Min Du, Qingdong Zhang, Danrong Lu, Yingying Xu, Xiangyu Xu, Wenshuang Wang, Yu-Zhong Zhang, Fuchuan Li
Glycosaminoglycan (GAG) lyases are often strictly substrate specific, and it is especially difficult to simultaneously degrade GAGs with different types of glycosidic bonds. Herein, we found a new class of GAG lyases (GAGases) from different bacteria. These GAGases belong to polysaccharide lyase 35 family and share quite low homology with the identified GAG lyases. The most surprising thing is that
-
USP36 inhibits apoptosis by deubiquitinating cIAP1 and survivin in colorectal cancer cells J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Bao Gao, Yuan Qiao, Shan Zhu, Ning Yang, Shan-Shan Zou, Yong-Jun Liu, Jingtao Chen
Chemotherapeutic agents for treating colorectal cancer (CRC) primarily induce apoptosis in tumor cells. The ubiquitin-proteasome system is critical for apoptosis regulation. Deubiquitinating enzymes (DUBs) remove ubiquitin from substrates to reverse ubiquitination. Although over 100 DUB members have been discovered, the biological functions of only a small proportion of DUBs have been characterized
-
Smad7 palmitoylation by the S-acyltransferase zDHHC17 enhances its inhibitory effect on TGF-β/Smad signaling J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Oleksandr Voytyuk, Yae Ohata, Aristidis Moustakas, Peter ten Dijke, Carl-Henrik Heldin
Intracellular signaling by the pleiotropic cytokine transforming growth factor-β (TGF-β) is inhibited by Smad7 in a feedback control mechanism. The activity of Smad7 is tightly regulated by multiple post-translational modifications. Using resin-assisted capture and metabolic labeling methods, we show here that Smad7 is S-palmitoylated in mammary epithelial cell models that are widely studied because
-
Dynamic stem–loop extension by Pol θ and templated insertion during DNA repair J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Denisse Carvajal-Maldonado, Yuzhen Li, Mark Returan, April M. Averill, Sylvie Doublié, Richard D. Wood
Theta-mediated end joining (TMEJ) is critical for survival of cancer cells when other DNA double-stranded break repair pathways are impaired. Human DNA polymerase theta (Pol θ) can extend ssDNA oligonucleotides, but little is known about preferred substrates and mechanism. We show that Pol θ can extend both ssDNA and RNA substrates by unimolecular stem–loop synthesis initiated by only two 3ʹ terminal
-
Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-12 Shun Matsumura, Christina Signoretti, Samuel Fatehi, Bat Ider Tumenbayar, Catherine D’Addario, Erik Nimmer, Colin Thomas, Trisha Viswanathan, Alexandra Wolf, Victor Garcia, Petra Rocic, Yongho Bae, SM Shafiqul Alam, Sachin A. Gupte
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased , glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs
-
Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-10 Julian von Ehr, Lasse Oberstrass, Ege Yazgan, Lara Ina Schnaubelt, Nicole Blümel, Francois McNicoll, Julia E. Weigand, Kathi Zarnack, Michaela Müller-McNicoll, Sophie Marianne Korn, Andreas Schlundt
AT-rich interacting domain (ARID)-containing proteins, Arids, are a heterogeneous DNA-binding protein family involved in transcription regulation and chromatin processing. For the member Arid5a, no exact DNA-binding preference has been experimentally defined so far. Additionally, the protein binds to mRNA motifs for transcript stabilization, supposedly through the DNA-binding ARID domain. To date,
-
The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-10 Mandira Dutta, Yuan Su, Caroline B. Plescia, Gregory A. Voth, Robert V. Stahelin
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a lipid-enveloped virus that acquires its lipid bilayer from the host cell it infects. SARS-CoV-2 can spread from cell to cell or from patient to patient by undergoing assembly and budding to form new virions. The assembly and budding of SARS-CoV-2 is mediated by several structural proteins known as envelope (E), membrane (M), nucleoprotein
-
RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-08 Mutsuko Kukimoto-Niino, Kazushige Katsura, Yoshiko Ishizuka-Katsura, Chiemi Mishima-Tsumagari, Mayumi Yonemochi, Mio Inoue, Reiko Nakagawa, Rahul Kaushik, Kam Y.J. Zhang, Mikako Shirouzu
The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EM structures of the DOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition
-
A novel series of metazoan L/D peptide isomerases J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-08 Harvey M. Andersen, Hua-Chia Tai, Stanislav S. Rubakhin, Peter M. Yau, Jonathan V. Sweedler
The function of endogenous cell-cell signaling peptides relies on their interactions with cognate receptors, which in turn are influenced by the peptides' structures, necessitating a comprehensive understanding of the suite of post-translational modifications of the peptide. Herein, we report the initial characterization of putative peptide isomerase enzymes extracted from , , and tissues. These enzymes
-
Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-07 Thomas M. Hallam, Anneliza Andreadi, Scott J. Sharp, Vicky Brocklebank, Emanuela Gardenal, Anna Dreismann, SCOPE Study Group, Rashi Arora, Marcus Dennis, Christina Flaxel, Edward Hall, Carel Hoyng, Peter Charbel Issa, Nicolas Leveziel, Fanni Molnár, Rafael Navarro, Todd Schneiderman, David Steel, Ramin Tadayoni, Tongalp Tezel, Michel Weber, Andrew J. Lotery, Kevin J. Marchbank, Claire L. Harris, Amy
Rare variants (RVs) in the gene encoding the regulatory enzyme complement factor I (; FI) that reduce protein function or levels increase age-related macular degeneration risk. A total of 3357 subjects underwent screening in the SCOPE natural history study for geographic atrophy secondary to age-related macular degeneration, including sequencing followed by serum FI measurement. Eleven RV genotypes
-
Discovery of an antivirulence compound that targets the Staphylococcus aureus SaeRS two-component system to inhibit toxic shock syndrome toxin-1 production J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-07 Karine Dufresne, Dennis A. DiMaggio Jr., Carla S. Maduta, Shaun R. Brinsmade, John K. McCormick
Menstrual toxic shock syndrome (mTSS) is a rare but severe disorder associated with the use of menstrual products such as high-absorbency tampons and is caused by strains that produce the toxic shock syndrome toxin-1 (TSST-1) superantigen. Herein, we screened a library of 3920 small bioactive molecules for the ability to inhibit transcription of the TSST-1 gene without inhibiting the growth of . The
-
Crosslinking of base-modified RNAs by synthetic DYW-KP base editors implicates an enzymatic lysine as the nitrogen donor for U-to-C RNA editing J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-07 Michael L. Hayes, Elvin T. Garcia, Skellie O. Chun, Matthias Selke
Base editing mechanisms are being investigated as potential therapeutic tools to alleviate genetic diseases. Sequence-specific cytidine to uridine (C-to-U) and adenosine to inosine base editing tools are capable of altering RNA and DNA sequences and utilize a hydrolytic deamination mechanism requiring an active site zinc ion and a glutamate residue. In plant organelles, DYW-PG domain containing enzymes
-
Identification of a conserved G-quadruplex within the E165R of African swine fever virus (ASFV) as a potential antiviral target J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-07 Wenhao Liu, Xinglin He, Yance Zhu, Yaqin Li, Zhihao Wang, Pengfei Li, Jiajia Pan, Jiang Wang, Beibei Chu, Guoyu Yang, Mengjia Zhang, Qigai He, Yongtao Li, Wentao Li, Chao Zhang
Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory
-
Interdomain communication in a homodimeric ABC transporter J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-05 Katharina-Astrid Lindt, Stefan Frühschulz, Robert Tampé, Rupert Abele
ABC transporters are found in all organisms and almost every cellular compartment. They mediate the transport of various solutes across membranes, energized by ATP binding and hydrolysis. Dysfunctions can result in severe diseases, such as cystic fibrosis or antibiotic resistance. In type IV ABC transporters, each of the two nucleotide-binding domains is connected to a transmembrane domain by two coupling
-
Mechanistic insights into complement pathway inhibition by CR1 domain duplication J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Sandra Wymann, Anup G. Nair, Svenja Ewert, Glenn A. Powers, Soo San Wan, Matthias Pelzing, Adriana Baz Morelli, Tony Rowe, Matthew P. Hardy
Complement receptor 1 (CR1) is a membrane glycoprotein with a highly duplicated domain structure able to bind multiple ligands such as C3b and C4b, the activated fragments of complement components C3 and C4, respectively. We have previously used our knowledge of this domain structure to identify CSL040, a soluble extracellular fragment of CR1 containing the long homologous repeat (LHR) domains A, B
-
LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Yuko Tokoro, Masamichi Nagae, Miyako Nakano, Anne Harduin-Lepers, Yasuhiko Kizuka
Structural variation of -glycans is essential for the regulation of glycoprotein functions. GalNAcβ1–4GlcNAc (LacdiNAc or LDN), a unique subterminal glycan structure synthesized by B4GALNT3 or B4GALNT4, is involved in the clearance of -glycoproteins from the blood and maintenance of cell stemness. Such regulation of glycoprotein functions by LDN is largely different from that by the dominant subterminal
-
Epidermal keratinocytes regulate hyaluronan metabolism via extracellularly secreted hyaluronidase 1 and hyaluronan synthase three J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Minori Abe, Manami Masuda, Yoichi Mizukami, Shintaro Inoue, Yukiko Mizutani
Hyaluronan (HA) is a high-molecular-weight (HMW) glycosaminoglycan, which is a fundamental component of the extracellular matrix that is involved in a variety of biological processes. We previously showed that the HYBID/KIAA1199/CEMIP axis plays a key role in the depolymerization of HMW-HA in normal human dermal fibroblasts (NHDFs). However, its roles in normal human epidermal keratinocytes (NHEKs)
-
The ubiquitin E3 ligase APC/CCdc20 mediates mitotic degradation of OGT J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Li Meng, Rui Dong, Weixiao Mi, Ke Qin, Kunfu Ouyang, Jianwei Sun, Jing Li
O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is the sole enzyme that catalyzes all O-GlcNAcylation reactions intracellularly. Previous investigations have found that OGT levels oscillate during the cell division process. Specifically, OGT abundance is downregulated during mitosis, but the underlying mechanism is lacking. Here we demonstrate that OGT is ubiquitinated by the ubiquitin
-
PPARα phosphorylation regulates colorectal tumor immune escape J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Qian Gou, Xiaoqing Tian, Chen Dong, Bingjun Yan, Mingjun Chen, Juanjuan Shi, Limin Yang, Yongzhong Hou
A high level of PD-L1 in cancer cells promotes tumor immune escape and inhibits tumor immunotherapy. Although PD-L1 gene expression is upregulated by multiple pathways, its gene transcriptional repression is still unclear. Here we found that loss of PPARα, one of the peroxisome-proliferator-activated receptors (PPARs) family members, promoted colorectal tumor immune escape. Mechanistically, PPARα directly
-
Mutations in tyrosyl-DNA phosphodiesterase 2 suppress top-2 induced chromosome segregation defects during Caenorhabditis elegans spermatogenesis J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Ji Kent Kwah, Nirajan Bhandari, Christine Rourke, Gabriella Gassaway, Aimee Jaramillo-Lambert
Meiosis reduces ploidy through two rounds of chromosome segregation preceded by one round of DNA replication. In meiosis I, homologous chromosomes segregate, while in meiosis II, sister chromatids separate from each other. Topoisomerase II (Topo II) is a conserved enzyme that alters DNA structure by introducing transient double-strand breaks. During mitosis, Topo II relieves topological stress associated
-
Poglut2/3 double knockout in mice results in neonatal lethality with reduced levels of fibrillin in lung tissues J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Sanjiv Neupane, Daniel B. Williamson, Robyn A. Roth, Carmen M. Halabi, Robert S. Haltiwanger, Bernadette C. Holdener
Fibrillin microfibrils play a critical role in the formation of elastic fibers, tissue/organ development, and cardiopulmonary function. These microfibrils not only provide structural support and flexibility to tissues, but they also regulate growth factor signaling through a plethora of microfibril-binding proteins in the extracellular space. Mutations in fibrillins are associated with human diseases
-
To each its own: Mechanisms of cross-talk between GPI biosynthesis and cAMP-PKA signaling in Candida albicans versus Saccharomyces cerevisiae J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Sneha Sudha Komath
-
LRRC8/VRAC volume-regulated anion channels are crucial for hearing J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-04 Deborah A. Knecht, Mariia Zeziulia, Mit B. Bhavsar, Dmytro Puchkov, Hannes Maier, Thomas J. Jentsch
Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters. Ablation of ClC‑K/barttin chloride channels causes deafness by interfering with the positive electrical potential of the endolymph, but roles of other anion channels in the inner ear have not been studied. Here we report the intracochlear
-
A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Jia Li, Lin Leng, Georgios Pantouris, Ramu Manjula, Marta Piecychna, Laura Abriola, Buqu Hu, Elias Lolis, Michelle E. Armstrong, Seamas C. Donnelly, Richard Bucala
Functional variants of the gene for the cytokine macrophage migration inhibitory factor (MIF) are defined by a 4-nucleotide promoter microsatellite (−794 CATT, rs5844572) and confer risk for autoimmune, infectious, and oncologic diseases. We describe herein the discovery of a prototypic, small molecule inhibitor of transcription with selectivity for high microsatellite repeat number and correspondingly
-
A spatial portrait of the human sebaceous gland transcriptional program J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Maria Schmidt, Florian Hansmann, Henry Loeffler-Wirth, Christos C. Zouboulis, Hans Binder, Marlon R. Schneider
Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead
-
Transmembrane helix interactions regulate oligomerization of the receptor tyrosine kinase EphA2 J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Daniel Wirth, Ece Özdemir, William C. Wimley, Elena B. Pasquale, Kalina Hristova
The transmembrane helices of receptor tyrosine kinases (RTKs) have been proposed to switch between two different dimeric conformations, one associated with the inactive RTK and the other with the active RTK. Furthermore, recent work has demonstrated that some full-length RTKs are associated with oligomers that are larger than dimers, raising questions about the roles of the TM helices in the assembly
-
2.5A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9 J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Dhritiman Dey, Rudra Chakravarti, Oindrila Bhattacharjee, Satyabrata Majumder, Dwaipayan Chaudhuri, Kazi Tawsif Ahmed, Dipanjan Roy, Bireswar Bhattacharya, Mansi Arya, Anupam Gautam, Rajveer Singh, Rahul Gupta, Velayutham Ravichandiran, Dhrubajyoti Chattopadhyay, Abhrajyoti Ghosh, Kalyan Giri, Syamal Roy, Dipanjan Ghosh
The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand. In order
-
Three prime repair exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural, and conformational properties J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Prem Prakash, Purva Khodke, Muthukumar Balasubramaniam, Benem-Orom Davids, Thomas Hollis, Jamaine Davis, Bajarang Kumbhar, Chandravanu Dash
HIV-1 integration into the human genome is dependent on 3′-processing of the viral DNA. Recently, we reported that the cellular Three Prime Repair Exonuclease 1 (TREX1) enhances HIV-1 integration by degrading the unprocessed viral DNA, while the integration-competent 3′-processed DNA remained resistant. Here, we describe the mechanism by which the 3′-processed HIV-1 DNA resists TREX1-mediated degradation
-
Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-03 Maya M. Polovitskaya, Tanushka Rana, Kurt Ullrich, Simona Murko, Tatjana Bierhals, Guido Vogt, Tobias Stauber, Christian Kubisch, René Santer, Thomas J. Jentsch
Together with its β-subunit OSTM1, ClC-7 performs 2Cl/H exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis and lysosomal storage. variants can cause recessive or dominant disease. Different variants entail different sets of symptoms. Loss of ClC-7 causes osteopetrosis and mostly neuronal lysosomal storage. A recently reported
-
Exploration of the binding determinants of protein phosphatase 5 (PP5) reveals a chaperone-independent activation mechanism J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-01 Shweta Devi, Annemarie Charvat, Zoe Millbern, Nelson Vinueza, Jason E. Gestwicki
The protein phosphatase 5 (PP5) is normally recruited to its substrates by the molecular chaperones, heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90). This interaction requires the tetratricopeptide repeat (TPR) domain of PP5, which binds to an EEVD motif at the extreme C termini of cytosolic Hsp70 and Hsp90 isoforms. In addition to bringing PP5 into proximity with chaperone-bound substrates
-
Circadian control of histone turnover during cardiac development and growth J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-01 Adrian Arrieta, Douglas J. Chapski, Anna Reese, Todd H. Kimball, Kunhua Song, Manuel Rosa-Garrido, Thomas M. Vondriska
During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting a role for the circadian clock in temporal control of histone turnover and coordinated
-
Polymerizing laminins in development, health, and disease J. Biol. Chem. (IF 4.0) Pub Date : 2024-06-01 Peter D. Yurchenco, Arkadiusz W. Kulczyk
Polymerizing laminins are multi-domain basement membrane (BM) glycoproteins that self-assemble into cell-anchored planar lattices to establish the initial BM scaffold. Nidogens, collagen-IV and proteoglycans then bind to the scaffold at different domain loci to create a mature BM. The LN domains of adjacent laminins bind to each other to form a polymer node, while the LG domains attach to cytoskeletal-anchoring
-
Three dimensional and four dimensional live imaging to study mechanisms of progressive neurodegeneration J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Jeremy W. Linsley, Terry Reisine, Steven Finkbeiner
Neurodegenerative diseases are complex and progressive, posing challenges to their study and understanding. Recent advances in microscopy imaging technologies have enabled the exploration of neurons in three spatial dimensions (3D) over time (4D). When applied to 3D cultures, tissues, or animals, these technologies can provide valuable insights into the dynamic and spatial nature of neurodegenerative
-
Small molecule MarR modulators potentiate metronidazole antibiotic activity in aerobic E. coli by inducing activation by the nitroreductase NfsA J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Thibault Caradec, Coline Plé, Giuseppe Sicoli, Ravil Petrov, Elizabeth Pradel, Cécilia Sobieski, Rudy Antoine, Maylis Orio, Adrien Herledan, Nicolas Willand, Ruben Christiaan Hartkoorn
Antibiotic-resistant pose a major threat to healthcare systems worldwide, necessitating the development of novel strategies to fight such hard-to-kill bacteria. One potential approach is to develop molecules that force bacteria to hyper-activate prodrug antibiotics, thus rendering them more effective. In the present work, we aimed to obtain proof-of-concept data to support that small molecules targeting
-
Distinct roles of the major binding residues in the cation-binding pocket of the melibiose transporter MelB J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Parameswaran Hariharan, Amirhossein Bakhtiiari, Ruibin Liang, Lan Guan
serovar Typhimurium melibiose permease (MelB) is a prototype of the major facilitator superfamily (MFS) transporters, which play important roles in human health and diseases. MelB catalyzed the symport of galactosides with Na, Li, or H but prefers the coupling with Na. Previously, we determined the structures of the inward- and outward-facing conformation of MelB and the molecular recognition for galactoside
-
Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N. Berry, Conor McClenaghan, Alyssa J. Foy, Alex Hanson, Deborah F. Steinberg, Jessica A. Greven, Colin E. Kluender, Jennifer M. Alexander-Brett, Colin G. Nichols, Tom J. Brett
The Ca-activated Cl channel regulator CLCA1 potentiates the activity of the Ca-activated Cl channel (CaCC) TMEM16A by directly engaging the channel at the cell surface, inhibiting its reinternalization and increasing Ca-dependent Cl current (I) density. We now present evidence of functional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC TMEM16B. Similar
-
Disordered region of nuclear membrane protein Bqt4 recruits phosphatidic acid to the nuclear envelope to maintain its structural integrity J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Yasuhiro Hirano, Tsukino Sato, Ayane Miura, Yoshino Kubota, Tomoko Shindo, Koichi Fukase, Tatsuo Fukagawa, Kazuya Kabayama, Tokuko Haraguchi, Yasushi Hiraoka
The nuclear envelope (NE) is a permeable barrier that maintains nuclear–cytoplasmic compartmentalization and ensures nuclear function; however, it ruptures in various situations such as mechanical stress and mitosis. Although the protein components for sealing a ruptured NE have been identified, the mechanism by which lipid components are involved in this process remains to be elucidated. Here, we
-
Intestinal lysozyme engagement of Salmonella Typhimurium stimulates the release of barrier-impairing InvE and Lpp1 J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-31 Jiangmeng Han, Iyshwarya Balasubramanian, Juan A. Flores, Sheila Bandyopadhyay, Jiaxing Yang, Yue Liu, Rajbir Singh, Prashanth Setty, Pawel Kiela, Ronaldo Ferraris, Nan Gao
Lysozyme is a β-1,4-glycosidase that hydrolyzes the polysaccharide backbone of bacterial cell walls. With an additional bactericidal function mediated by a separate protein domain, lysozyme is considered a uniquely important antimicrobial molecule contributing to the host's innate immune response to infection. Elevated lysozyme production is found in various inflammatory conditions while patients with
-
Lipid switches in the immunological synapse J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-30 Gillian Griffiths, Britta Brügger, Christian Freund
Adaptive immune responses comprise the activation of T cells by peptide antigens that are presented by proteins of the Major Histocompatibility Complex (MHC) on the surface of an antigen-presenting cell. As a consequence of the T cell receptor interacting productively with a certain peptide-MHC complex, a specialized cell-cell junction known as the immunological synapse forms and is accompanied by
-
Circular RNA circMYLK4 shifts energy metabolism from glycolysis to OXPHOS by binding to the calcium channel auxiliary subunit CACNA2D2 J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-30 Haigang Cao, Chenchen Li, Xiaohui Sun, Jinjin Yang, Xiao Li, Gongshe Yang, Jianjun Jin, Xine Shi
Skeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation. The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics
-
A crucial role of adenosine deaminase in regulating gluconeogenesis in mice J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-30 Zhao Ding, Wenhao Ge, Xiaogang Xu, Xiaodong Xu, Qi Sun, Xi Xu, Jianfa Zhang
Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine (ADO) to inosine and regulates ADO concentration. ADA ubiquitously expresses in various tissues to mediate ADO-receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus. Here, we show that elevated plasma ADA activity is a compensated
-
Molecular determinants of Ras-mTORC2 signaling J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Stephen F. Smith, A.F.M. Tariqul Islam, Shoxruxxon Alimukhamedov, Ethan T. Weiss, Pascale G. Charest
Recent research has identified the mechanistic Target of Rapamycin Complex 2 (mTORC2) as a conserved direct effector of Ras proteins. While previous studies suggested the involvement of the Switch I (SWI) effector domain of Ras in binding mTORC2 components, the regulation of the Ras-mTORC2 pathway is not entirely understood. In , mTORC2 is selectively activated by the Ras protein RasC, and the RasC-mTORC2
-
STIM1-dependent store-operated calcium entry mediates sex differences in macrophage chemotaxis and monocyte recruitment J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Adriana M. Fresquez, James O. Hogan, Patricia Rivera, Kristen M. Patterson, Kanakadurga Singer, Joseph M. Reynolds, Carl White
Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of directed cell movement toward a chemical signal. The mechanisms governing sexual dimorphism in chemotaxis are not known. We hypothesized a role for the store-operated calcium entry (SOCE) pathway in regulating chemotaxis by modulating leading
-
Fidelity in plant hormone modifications catalyzed by Arabidopsis GH3 acyl acid amido synthetases J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Cynthia K. Holland, Joseph M. Jez
GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetases conjugate amino acids to acyl acid hormones to either activate or inactivate the hormone molecule. The largest subgroup of GH3 proteins modify the growth-promoting hormone auxin (indole-3-acetic acid; IAA) with the second largest class activating the defense hormone jasmonic acid (JA). The two-step reaction mechanism of GH3 proteins provides a potential
-
Klebsiella pneumoniae O-polysaccharide biosynthesis highlights the diverse organization of catalytic modules in ABC transporter-dependent glycan assembly J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Steven D. Kelly, Danielle M. Williams, Shawna Zhu, Taeok Kim, Manas Jana, Jeremy Nothof, V. Narasimharao Thota, Todd L. Lowary, Chris Whitfield
provides influential prototypes for lipopolysaccharide O antigen (OPS) biosynthesis in Gram-negative bacteria. Sequences of OPS-biosynthesis gene clusters in serotypes O4 and O7 suggest fundamental differences in the organization of required enzyme modules compared to other serotypes. Furthermore, some required activities were not assigned by homology shared with characterized enzymes. The goal of
-
Neuronal activity promotes secretory autophagy for the extracellular release of α-synuclein J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Yoshitsugu Nakamura, Taiki Sawai, Kensuke Kakiuchi, Shigeki Arawaka
Extracellular secretion is an essential mechanism for α-synuclein (α-syn) proteostasis. Although it has been reported that neuronal activity affects α-syn secretion, the underlying mechanisms remain unclear. Here, we investigated the autophagic processes that regulate the physiological release of α-syn in mouse primary cortical neurons and SH-SY5Y cells. Stimulating neuronal activity with glutamate
-
ACLY alternative splicing correlates with cancer phenotypes J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Julianna G. Supplee, Hayley C. Affronti, Richard Duan, Rebekah C. Brooks, Zachary E. Stine, Phuong T.T. Nguyen, Laura V. Pinheiro, Michael C. Noji, Jack M. Drummond, Kevin Huang, Kollin Schultz, Chi V. Dang, Ronen Marmorstein, Kathryn E. Wellen
ATP-citrate lyase (ACLY) links carbohydrate and lipid metabolism and provides nucleocytosolic acetyl-CoA for protein acetylation. has two major splice isoforms: the full-length canonical “long” isoform and an uncharacterized “short” isoform in which exon 14 is spliced out. Exon 14 encodes 10 amino acids within an intrinsically disordered region and includes at least one dynamically phosphorylated residue
-
Multi-modal mechanisms of the metastasis suppressor, NDRG1: Inhibition of WNT/β-catenin signaling by stabilization of protein kinase Cα J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Mahan Gholam Azad, Mohammed Hussaini, Tiffany M. Russell, Vera Richardson, Busra Kaya, Mahendiran Dharmasivam, Des R. Richardson
The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), inhibits pro-oncogenic signaling in pancreatic cancer (PC). This investigation dissected a novel mechanism induced by NDRG1 on WNT/β-catenin signaling in multiple PC cell types. NDRG1 overexpression decreased β-catenin and downregulated glycogen synthase kinase-3β (GSK-3β) protein levels and its activation. However, β-catenin phosphorylation
-
ATXN3 functions as a tumor suppressor through potentiating galectin-9-mediated apoptosis in human colon adenocarcinoma J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-28 Yang Cheng, Shengnan Wang, Qiong Gao, Deyu Fang
While deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect in human colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both and in xenograft
-
CTCF and BORIS-mediated autophagy regulation via alternative splicing of BNIP3L in breast cancer J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-27 Anchala Pandey, Parik Kakani, Sanjeev Shukla
Autophagy is a pivotal regulatory and catabolic process, induced under various stressful conditions, including hypoxia. However, little is known about alternative splicing of autophagy genes in the hypoxic landscape in breast cancer. Our research unravels the hitherto unreported alternative splicing of BNIP3L, a crucial hypoxia-induced autophagic gene. We showed that BNIP3L, under hypoxic condition
-
Splicing factor hnRNPA1 regulates alternative splicing of LOXL2 to enhance the production of LOXL2Δ13 J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-27 Deyuan Pan, Lin Long, Chengyu Li, Yingxin Zhou, Qing Liu, Ziting Zhao, Hui Zhao, Wan Lin, Zhenyuan Zheng, Liu Peng, Enmin Li, Liyan Xu
Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and has the ability to catalyze the cross-linking of extracellular matrix collagen and elastin. High expression of LOXL2 is related to tumor cell proliferation, invasion, and metastasis. contains 14 exons. Previous studies have found that has abnormal alternative splicing and exon skipping in a variety of tissues and cells, resulting
-
PolyQ-expanded ataxin-2 aggregation impairs cellular processing-body homeostasis via sequestering the RNA helicase DDX6 J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-27 Jian-Yang Wang, Ya-Jun Liu, Xiang-Le Zhang, Yin-Hu Liu, Lei-Lei Jiang, Hong-Yu Hu
Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence
-
Correction: Discovery, structure, mechanisms, and evolution of protein-only RNase P enzymes J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-25 Walter Rossmanith, Philippe Giegé, Roland K. Hartmann
-
Reciprocal regulation of cardiac β-oxidation and pyruvate dehydrogenase by insulin J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-23 Abdallah Elnwasany, Heba A. Ewida, Ivan Menendez-Montes, Monika Mizerska, Xiaorong Fu, Chai-Wan Kim, Jay D. Horton, Shawn C. Burgess, Beverly A. Rothermel, Pamela A. Szweda, Luke I. Szweda
The heart alters the rate and relative oxidation of fatty acids and glucose based on availability and energetic demand. Insulin plays a crucial role in this process diminishing fatty acid and increasing glucose oxidation when glucose availability increases. Loss of insulin sensitivity and metabolic flexibility can result in cardiovascular disease. It is therefore important to identify mechanisms by
-
An upstream enhancer and MEF2 transcription factors fine-tune the regulation of the Bdnf gene in cortical and hippocampal neurons J. Biol. Chem. (IF 4.0) Pub Date : 2024-05-23 Annela Avarlaid, Kaisa Falkenberg, Karin Lehe, Giuseppa Mudò, Natale Belluardo, Valentina Di Liberto, Monica Frinchi, Jürgen Tuvikene, Tõnis Timmusk
The myocyte enhancer factor (MEF2) family of transcription factors, originally discovered for its pivotal role in muscle development and function, has emerged as an essential regulator in various aspects of brain development and neuronal plasticity. The MEF2 transcription factors are known to regulate numerous important genes in the nervous system, including brain-derived neurotrophic factor (BDNF)