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The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-\u03b1) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>To better understand the relationship between pVHL and aPKC, the PKC iota (PKC\u03b9) isoform of aPKC was knocked out in renal carcinoma cells, both pVHL-negative and those with replaced pVHL. Cellular properties associated with pVHL function were assayed. Knockout of PKC\u03b9 in pVHL-expressing cells led to greater downregulation of HIF-\u03b1 than seen with pVHL alone, suggesting that the presence of PKC\u03b9 opposes complete regulation of HIF-\u03b1 by pVHL. In contrast, absence of either pVHL or PKC\u03b9 disrupted tight junction formation and led to upregulated levels of \u03b15 integrin, both of which were phenocopied by lysosomal inhibition. LAMP1 (lysosome associated membrane protein 1), a marker for lysosomes, showed dysregulated localization and altered electrophoretic gel migration in the absence of pVHL. While the upregulated \u03b15 integrin seen in the absence of either pVHL or PKC\u03b9 loss was associated with increased cell adhesion, loss of pVHL caused increased cell motility whereas loss of PKC\u03b9 decreased motility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data are consistent with a known role of PKC\u03b9 in endocytosis of \u03b15 integrin and suggest a subsequent novel role of pVHL in targeting a pool of endocytosed \u03b15 integrin for lysosomal degradation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-025-10272-1","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T04:09:47Z","timestamp":1738210187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein kinase C iota (PKC\u03b9) and pVHL are both needed for lysosomal degradation of \u03b15 integrin in renal carcinoma cells"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8669-0783","authenticated-orcid":false,"given":"Alissa F.","family":"Schurr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandni S.","family":"Dave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi J.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Meth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria S.","family":"Jaramillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Bartley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6778-1548","authenticated-orcid":false,"given":"Alan R.","family":"Schoenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"10272_CR1","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1126\/science.8493574","volume":"260","author":"F Latif","year":"1993","unstructured":"Latif F, Tory K, Gnarra J et al (1993) Identification of the Von Hippel-Lindau disease tumor suppressor gene. 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