Liu W-T, Huang K-Y, Lu M-C, Huang H-L, Chen C-Y, Cheng Y-L, Yu H-C, Liu S-Q, Lai N-S, Huang H-B
Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.
Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.
Oncogene. 2017 May 11;36(19):2715-2723. doi: 10.1038/onc.2016.424. Epub 2016 Nov 28.
Crosstalk between transforming growth factor beta (TGF-β) signaling and p53 has a critical role in cancer progression. TGF-β signals via Smad and non-Smad pathways. Under normal conditions, wild-type p53 forms a complex with Smad2/3 and co-activates transcription of a variety of tumor suppressor genes, resulting in tumor suppressive effects. Thus, p53 stability is essential in progression of tumor suppressive responses mediated by TGF-β signaling. However, it remains unknown whether p53 stability is regulated by TGF-β. In the current study, we identify that USP15 binds to and stabilizes p53 through deubiquitination in U2OS and HEK293 cells. TGF-β promotes the translation of USP15 through activation of mammalian target of rapamycin by the phosphoinositide 3-kinase/AKT pathway. Upregulation of USP15 translation links the crosstalk between TGF-β signaling and p53 stability, allowing this cytokine to have a critical role in cancer progression.
转化生长因子β（TGF-β）信号传导与p53之间的相互作用在癌症进展中起关键作用。TGF-β通过Smad和非Smad途径发出信号。在正常情况下，野生型p53与Smad2/3形成复合物，并共同激活多种肿瘤抑制基因的转录，从而产生肿瘤抑制作用。因此，p53稳定性在TGF-β信号传导介导的肿瘤抑制反应进展中至关重要。然而，p53稳定性是否受TGF-β调节仍不清楚。在本研究中，我们发现在U2OS和HEK293细胞中，USP15通过去泛素化作用与p53结合并使其稳定。TGF-β通过磷酸肌醇3激酶/AKT途径激活雷帕霉素哺乳动物靶蛋白，从而促进USP15的翻译。USP15翻译的上调将TGF-β信号传导与p53稳定性之间的相互作用联系起来，使这种细胞因子在癌症进展中起关键作用。
Zotero 插件
