Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Key Laboratory of Pathophysiology of Zhejing Province, Ningbo 315211, Zhejiang, China
Abstract:Protein post-translational modification is a precondition guaranteeing normal exertion of protein functions. Ubiquitination is an important post-translational modification that maintains normal protein levels and activity. Numerous researches show that the E3 ubiquitin ligase speckle-type POZ protein (SPOP) displays mutations in many tumors and genetic diseases. Mainly concentrated in the MATH structural domain that recognizes substrates, these mutations influence the binding between SPOP and substrates, and further influence their protein levels, positioning and activities, thus disturbing the normal physiological functions. Wild-type SPOP binds the substrates, most of which enter the proteasome pathway for decomposition after being ubiquitinated by SPOP, but some substrates are also influenced functionally. Herein we review the ubiquitination types and functions of SPOP substrates, including the ubiquitin-proteasome system (UPS), structure, functions and molecular pathways of SPOP, and non-degradative ubiquitinated modification of SPOP. The emphasis will be laid on the molecular mechanisms of the signaling pathways mediated by the three non-degradative substrates of SPOP, that is, myeloid differentiation primary response gene 88 (MyD88)-mediated NF-κB pathway, X-chromosome silence signal pathway of histone macroH2A1 (macroH2A. 1 histone, macroH2A1), and inverted formin 2 (INF2)-mediated chondriokinesis pathway, in inhibiting tumorigenesis and development. We expect to provide a new perspective for precise targeted therapies of tumors.
林婷, 曹心怡, 金晓锋. E3泛素连接酶接头蛋白SPOP介导的底物非降解型泛素化修饰[J]. 中国生物化学与分子生物学报, 2021, 37(7): 874-882.
LIN Ting, CAO Xin-Yi, JIN Xiao-Feng. SPOP-mediated Non-degradative Ubiquitination. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(7): 874-882.
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