TY - JOUR
T1 - Deregulation of SPOP in Cancer
AU - Zhang, Hui
AU - Jin, Xiaofeng
AU - Huang, Haojie
N1 - Funding Information:
The authors thank all the investigators for their contributions to the understanding of biochemistry, physiology, and tumor biology of wild-type and mutated SPOP proteins. The authors apologize in advance for being unable to cite all the relevant references due to the word limits of the article. This work is partially funded by The National Natural Science Foundation of China (grant no.32270821), The Natural Science Foundation of Ningbo (grant no. 2021J065), The Fundamental Research Funds for the Provincial Universities of Zhejiang (grant no. SJLZ2022004), The K.C. Wong Magna Fund in Ningbo University (to X. Jin), and the Mayo Clinic Foundation (to H. Huang).
Publisher Copyright:
© 2022 American Association for Cancer Research.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - Speckle-type POZ protein (SPOP) is a substrate-binding adaptor of the CULLIN3/RING-box1 E3 ubiquitin ligase complex. SPOP is frequently mutated in prostate and endometrial cancers, whereas it is overexpressed in renal cell carcinoma (RCC). SPOP can mediate both degradable and nondegradable polyubiquitination of a number of substrates with diverse biological functions such as androgen receptor (AR), SRC-3, TRIM24, BRD4, PD-L1, 53BP1, GLP/G9a, c-Myc, SENP7, among others. Cancer-associated SPOP mutants often impair SPOP binding and polyubiquitination of its substrates to influence various cancer-relevant pathways, which include androgen/AR signaling, DNA repair and methylation, cellular stress surveillance, cancer metabolism, and immunity. Although SPOP is recognized as a tumor suppressor in prostate and endometrial cancers, it acts like an oncoprotein in RCC. This review provides an overview of the recent progress in understanding of the upstream regulators of SPOP and its downstream targets, highlights the significant impact of SPOP mutations and overexpression on cancer pathogenesis, and discusses the potential of targeting SPOP for cancer treatment.
AB - Speckle-type POZ protein (SPOP) is a substrate-binding adaptor of the CULLIN3/RING-box1 E3 ubiquitin ligase complex. SPOP is frequently mutated in prostate and endometrial cancers, whereas it is overexpressed in renal cell carcinoma (RCC). SPOP can mediate both degradable and nondegradable polyubiquitination of a number of substrates with diverse biological functions such as androgen receptor (AR), SRC-3, TRIM24, BRD4, PD-L1, 53BP1, GLP/G9a, c-Myc, SENP7, among others. Cancer-associated SPOP mutants often impair SPOP binding and polyubiquitination of its substrates to influence various cancer-relevant pathways, which include androgen/AR signaling, DNA repair and methylation, cellular stress surveillance, cancer metabolism, and immunity. Although SPOP is recognized as a tumor suppressor in prostate and endometrial cancers, it acts like an oncoprotein in RCC. This review provides an overview of the recent progress in understanding of the upstream regulators of SPOP and its downstream targets, highlights the significant impact of SPOP mutations and overexpression on cancer pathogenesis, and discusses the potential of targeting SPOP for cancer treatment.
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U2 - 10.1158/0008-5472.CAN-22-2801
DO - 10.1158/0008-5472.CAN-22-2801
M3 - Review article
C2 - 36512624
AN - SCOPUS:85148114249
SN - 0008-5472
VL - 83
SP - 489
EP - 499
JO - Cancer research
JF - Cancer research
IS - 4
ER -