{"id":7564,"date":"2012-10-20T10:05:54","date_gmt":"2012-10-20T09:05:54","guid":{"rendered":"http:\/\/www.ilmelanoma.com\/?p=7564"},"modified":"2026-10-16T10:44:23","modified_gmt":"2026-10-16T09:44:23","slug":"rhoj-pak-kinases-regulate-melanoma-chemoresistance","status":"publish","type":"post","link":"https:\/\/www.ilmelanoma.com\/en\/rhoj-pak-kinases-regulate-melanoma-chemoresistance\/","title":{"rendered":"RhoJ and Pak Kinases Regulate Melanoma Chemoresistance"},"content":{"rendered":"<p style=\"text-align: justify;\">Melanomas resist conventional chemotherapeutics in part through intrinsic disrespect of apoptotic checkpoint activation. In this study, using an unbiased genome-wide RNAi screen we identified RhoJ and its effector Pak1, as key modulators of melanoma cell sensitivity to DNA damage. We find that RhoJ activates Pak1 in response to drug-induced DNA damage, which then uncouples ATR from its downstream effectors, ultimately resulting in a blunted DNA damage response (DDR). In addition, ATR suppression leads to the decreased phosphorylation of ATF2, and consequent increased expression of the melanocyte survival gene Sox10 resulting in a higher DDR threshold required to engage melanoma cell death. In the setting of normal melanocyte behavior, this regulatory relationship may facilitate appropriate epidermal melanization in response to UV-induced DNA damage.<\/p>\n<p style=\"text-align: justify;\">Read more:\u00a0<a title=\"melanoma therapy\" href=\"https:\/\/cancerres.aacrjournals.org\/content\/early\/2012\/09\/12\/0008-5472.CAN-12-0775.abstract\" target=\"_blank\">RhoJ and Pak Kinases Regulate Melanoma Chemoresistance by Suppressing Pathways that Sense DNA Damage<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Melanomas resist conventional chemotherapeutics in part through intrinsic disrespect of apoptotic checkpoint activation. In this study, using an unbiased genome-wide RNAi screen we identified RhoJ and its effector Pak1, as key modulators of melanoma cell sensitivity to DNA damage. We find that RhoJ activates Pak1 in response to drug-induced DNA damage, which then uncouples ATR [&hellip;]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-7564","post","type-post","status-publish","format-standard","hentry","category-cura-melanoma"],"_links":{"self":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7564","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/comments?post=7564"}],"version-history":[{"count":1,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7564\/revisions"}],"predecessor-version":[{"id":10760,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7564\/revisions\/10760"}],"wp:attachment":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/media?parent=7564"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/categories?post=7564"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/tags?post=7564"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}