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In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
The ubiquitin code of RAS proteins: Decoding its role in cancer progression
Yedan Shi1,2,3, Yong Shen1,2,4, Xiuyuan Zhang1,2,3
1Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
None:
RAS proteins, as the most frequently mutated oncoproteins in human cancers, drive tumor proliferation, metastasis, and therapeutic resistance. Recent studies have revealed that ubiquitination dynamically regulates the stability, membrane localization, and signaling transduction of RAS proteins, profoundly impacting their oncogenic functions. A series of ubiquitination sites, E3 ligases, deubiquitinases, and regulatory proteins are involved in RAS ubiquitination. We also analyze the heterogeneity of ubiquitination patterns across distinct RAS isoforms (KRAS4A, KRAS4B, NRAS, and HRAS) and their functional disparities in cancers. Targeting the ubiquitination pathway offers novel strategies to overcome RAS proteins. Future research should integrate protein structure analysis and high-throughput screening to develop specific ubiquitination modulators and explore combination RAS ubiquitination targeting strategies with RAS inhibitors or immunotherapy, aiming to overcome RAS-driven malignant phenotypes.
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