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The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-\u03baB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4\u2009+\u2009T cells from HAM\/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-\u03baB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.<\/jats:p>","DOI":"10.1038\/s41467-024-49737-5","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:03:01Z","timestamp":1719320581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein"],"prefix":"10.1038","volume":"15","author":[{"given":"Suchitra","family":"Mohanty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Suklabaidya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Lavorgna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-2726","authenticated-orcid":false,"given":"Takaharu","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyater","family":"Ngouth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-6765","authenticated-orcid":false,"given":"Edward W.","family":"Harhaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"49737_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","volume":"3","author":"A Gessain","year":"2012","unstructured":"Gessain, A. & Cassar, O. 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