AI Article Synopsis
- SPOP is a key protein involved in regulating various cancer-related pathways, frequently mutated in prostate and endometrial cancers but overexpressed in renal cell carcinoma (RCC).
- SPOP's mutations can hinder its ability to bind and regulate important cancer-related proteins, affecting processes like hormone signaling and DNA repair.
- The review highlights the importance of understanding SPOP’s role in cancer development and explores the potential for targeting it in cancer therapies.
Article Abstract
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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| http://dx.doi.org/10.1158/0008-5472.CAN-22-2801 | DOI Listing |
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