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Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy.
The FEBS Journal ( IF 5.5 ) Pub Date : 2019-06-06 , DOI: 10.1111/febs.14952
Sweta Sikder 1 , Sujata Kumari 1 , Pallabi Mustafi 1 , Nisha Ramdas 2 , Swatishree Padhi 3 , Arka Saha 3 , Utsa Bhaduri 4 , Birendranath Banerjee 3 , Ravi Manjithaya 5 , Tapas K Kundu 1
The FEBS Journal ( IF 5.5 ) Pub Date : 2019-06-06 , DOI: 10.1111/febs.14952
Sweta Sikder 1 , Sujata Kumari 1 , Pallabi Mustafi 1 , Nisha Ramdas 2 , Swatishree Padhi 3 , Arka Saha 3 , Utsa Bhaduri 4 , Birendranath Banerjee 3 , Ravi Manjithaya 5 , Tapas K Kundu 1
Affiliation
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Multifunctional human transcriptional positive co-activator 4 (PC4) is a bona fide nonhistone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression causes a drastic decompaction which leads to open conformation of the chromatin, and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation, possibly through enhanced autophagic activity. Moreover, PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the ability of PC4 knockdown cells to survive. On the contrary, complementation with wild-type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in the absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during stress conditions such as radiation.
中文翻译：
非组蛋白人类染色质蛋白PC4对于基因组完整性至关重要，并负面调节自噬。
多功能人类转录阳性共激活因子4（PC4）是染色质的真正非组蛋白成分，在染色质紧实和功能性基因组组织过程中起着举足轻重的作用。抑制PC4表达会导致严重的失配，从而导致染色质的开放构象，从而改变核结构，改变染色体分离缺陷并改变表观遗传景观。有趣的是，这些缺陷不会诱导细胞死亡，但可能通过增强自噬活性而导致细胞增殖增强。此外，PC4耗尽对γ射线具有明显的抵抗力。暴露于伽玛射线进一步诱导了这些细胞中的自噬。小分子抑制剂以及关键自噬基因的沉默抑制自噬，大大降低了PC4敲低细胞存活的能力。相反，与野生型PC4互补可以逆转这种现象，从而证实了自噬过程是在不存在PC4的情况下抗辐射的关键机制。这些数据连接了染色质体系在调控辐射等应激条件下自噬过程中未曾探索的作用。
更新日期：2019-06-06
中文翻译：
非组蛋白人类染色质蛋白PC4对于基因组完整性至关重要，并负面调节自噬。
多功能人类转录阳性共激活因子4（PC4）是染色质的真正非组蛋白成分，在染色质紧实和功能性基因组组织过程中起着举足轻重的作用。抑制PC4表达会导致严重的失配，从而导致染色质的开放构象，从而改变核结构，改变染色体分离缺陷并改变表观遗传景观。有趣的是，这些缺陷不会诱导细胞死亡，但可能通过增强自噬活性而导致细胞增殖增强。此外，PC4耗尽对γ射线具有明显的抵抗力。暴露于伽玛射线进一步诱导了这些细胞中的自噬。小分子抑制剂以及关键自噬基因的沉默抑制自噬，大大降低了PC4敲低细胞存活的能力。相反，与野生型PC4互补可以逆转这种现象，从而证实了自噬过程是在不存在PC4的情况下抗辐射的关键机制。这些数据连接了染色质体系在调控辐射等应激条件下自噬过程中未曾探索的作用。
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