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Patients with copy number variants at this locus exhibit genitourinary tract anomalies. In this study, we show that decreased androgen receptor (AR) protein level correlated with increased AR ubiquitination in the testis of\n                    <jats:italic>Kctd13<\/jats:italic>\n                    \u2010deficient mice, suggesting that KCTD13 inhibits AR ubiquitination. KCTD13 increased CUL3\u2010dependent AR ubiquitination but had no effect on CUL3 binding to AR, confirming the role of KCTD13 as an adaptor of CUL3 ligase. Recombinant KCTD13 directly binds to recombinant AR, and the BTB domain of KCTD13 is critical for binding both the N\u2010terminal domain of AR and STUB1. Moreover, KCTD13 dose\u2010dependently decreased STUB1 binding to AR resulting in decreased AR ubiquitination. KCTD13 \u0394BTB was unable to bind to AR and subsequently failed to block STUB1\u2010mediated AR ubiquitination, strongly suggesting that reduced AR ubiquitination is dependent on KCTD13 ability to dissociate AR\/STUB1 complex. Furthermore, KCTD13 increased the expression of AR target gene,\n                    <jats:italic>FOXJ1<\/jats:italic>\n                    , whereas KCTD13 \u0394BTB had no effect. Our data reveal a distinctive mode of action of KCTD13 on AR ubiquitination depending on the E3 ubiquitin ligase involved: (1) KCTD13 increased CUL3\u2010dependent AR ubiquitination but had no effect on CUL3 binding to AR; and (2) KCTD13 decreased STUB1\u2010mediated AR ubiquitination by decreasing STUB1 binding to AR thus preventing AR ubiquitination. We hypothesize that in the testes of\n                    <jats:italic>Kctd13<\/jats:italic>\n                    \u2010deficient mice, the absence of KCTD13 results in increased binding of STUB1 to AR leading to increased AR ubiquitination and degradation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402072rr","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T06:19:23Z","timestamp":1739945963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Androgen receptor ubiquitination links\n                    <scp>KCTD13<\/scp>\n                    to genitourinary tract defects"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-4931","authenticated-orcid":false,"given":"Ahmed","family":"Chahdi","sequence":"first","affiliation":[{"name":"Department of Surgery Nemours Children's Health  Orlando Florida USA"},{"name":"College of Medicine 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