{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:27:31Z","timestamp":1776220051411,"version":"3.50.1"},"reference-count":139,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82072481"],"award-info":[{"award-number":["82072481"]}]},{"name":"National Natural Science Foundation of China","award":["81874223"],"award-info":[{"award-number":["81874223"]}]},{"name":"National Natural Science Foundation of China","award":["ZYJC21042"],"award-info":[{"award-number":["ZYJC21042"]}]},{"name":"1.3.5 project for disciplines of excellence (West China Hospital, Sichuan University)","award":["82072481"],"award-info":[{"award-number":["82072481"]}]},{"name":"1.3.5 project for disciplines of excellence (West China Hospital, Sichuan University)","award":["81874223"],"award-info":[{"award-number":["81874223"]}]},{"name":"1.3.5 project for disciplines of excellence (West China Hospital, Sichuan University)","award":["ZYJC21042"],"award-info":[{"award-number":["ZYJC21042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is a cullin 3-based E3 ubiquitin ligase adaptor protein that plays a crucial role in ubiquitin-mediated protein degradation. Recently, SPOP has attracted major research attention as it is frequently mutated in a range of cancers, highlighting pleiotropic tumorigenic effects and associations with treatment resistance. Structurally, SPOP contains a functionally critical N-terminal meprin and TRAF homology (MATH) domain for many SPOP substrates. SPOP has two other domains, including the internal Bric-a-brac-Tramtrack\/Broad (BTB) domain, which is linked with SPOP dimerization and binding to cullin3, and a C-terminal nuclear localization sequence (NLS). The dysregulation of SPOP-mediated proteolysis is associated with the development and progression of different cancers since abnormalities in SPOP function dysregulate cellular signaling pathways by targeting oncoproteins or tumor suppressors in a tumor-specific manner. SPOP is also involved in genome stability through its role in the DNA damage response and DNA replication. More recently, studies have shown that the expression of SPOP can be modulated in various ways. In this review, we summarize the current understanding of SPOP\u2019s functions in cancer and discuss how to design a rational therapeutic target.<\/jats:p>","DOI":"10.3390\/genes13112051","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"2051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["SPOP in Cancer: Phenomena, Mechanisms and Its Role in Therapeutic Implications"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiaojuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-5709","authenticated-orcid":false,"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nsmb.2793","article-title":"Cleaning up in the endoplasmic reticulum: Ubiquitin in charge","volume":"21","author":"Christianson","year":"2014","journal-title":"Nat. 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