eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer,Advanced Science

当前位置： X-MOL 学术 › Adv. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer
Advanced Science ( IF 14.3 ) Pub Date : 2023-08-06 , DOI: 10.1002/advs.202300759
Qihao Pan _{1,

2,

3,

4} , Fenghai Yu ₂ , Huilin Jin ₂ , Peng Zhang _{1,

2,

3} , Xiaoling Huang _{1,

2,

3} , Jingxuan Peng ₂ , Xiaoshan Xie ₂ , Xiangli Li ₂ , Ning Ma ₂ , Yue Wei ₂ , Weijie Wen ₂ , Jieping Zhang ₂ , Boyu Zhang _{1,

2,

3} , Hongyan Yu ₅ , Yuanxun Xiao ₆ , Ran-Yi Liu ₇ , Qingxin Liu _{1,

2,

3} , Xiangqi Meng _{1,

2,

3} , Mong-Hong Lee _{1,

2,

3,

8}

Affiliation

Numerous studies have demonstrated that individual proteins can moonlight. Eukaryotic Initiation translation factor 3, f subunit (eIF3f) is involved in critical biological functions; however, its role independent of protein translation in regulating colorectal cancer (CRC) is not characterized. Here, it is demonstrated that eIF3f is upregulated in CRC tumor tissues and that both Wnt and EGF signaling pathways are participating in eIF3f's oncogenic impact on targeting phosphoglycerate dehydrogenase (PHGDH) during CRC development. Mechanistically, EGF blocks FBXW7β-mediated PHGDH ubiquitination through GSK3β deactivation, and eIF3f antagonizes FBXW7β-mediated PHGDH ubiquitination through its deubiquitinating activity. Additionally, Wnt signals transcriptionally activate the expression of eIF3f, which also exerts its deubiquitinating activity toward MYC, thereby increasing MYC-mediated PHGDH transcription. Thereby, both impacts allow eIF3f to elevate the expression of PHGDH, enhancing Serine–Glycine–One–Carbon (SGOC) signaling pathway to facilitate CRC development. In summary, the study uncovers the intrinsic role and underlying molecular mechanism of eIF3f in SGOC signaling, providing novel insight into the strategies to target eIF3f-PHGDH axis in CRC.

中文翻译：

eIF3f 通过增强结直肠癌中的去泛素化活性来介导 SGOC 通路重编程

大量研究表明，单个蛋白质可以兼职。真核起始翻译因子 3，f 亚基 (eIF3f) 参与关键的生物学功能；然而，其在调节结直肠癌（CRC）中独立于蛋白质翻译的作用尚未得到表征。在此，证明 eIF3f 在 CRC 肿瘤组织中上调，并且 Wnt 和 EGF 信号通路都参与了 CRC 发育过程中 eIF3f 对靶向磷酸甘油酸脱氢酶 (PHGDH) 的致癌影响。从机制上讲，EGF 通过 GSK3β 失活阻断 FBXW7β 介导的 PHGDH 泛素化，而 eIF3f 通过其去泛素化活性拮抗 FBXW7β 介导的 PHGDH 泛素化。此外，Wnt 信号转录激活 eIF3f 的表达，eIF3f 也对 MYC 发挥其去泛素化活性，从而增加 MYC 介导的 PHGDH 转录。因此，这两种影响都使得 eIF3f 能够提高 PHGDH 的表达，增强丝氨酸-甘氨酸-单碳 (SGOC) 信号通路，从而促进 CRC 的发展。总之，该研究揭示了 eIF3f 在 SGOC 信号传导中的内在作用和潜在分子机制，为 CRC 中靶向 eIF3f-PHGDH 轴的策略提供了新的见解。

更新日期：2023-08-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南