{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nishiyama K"],"funding":["Takeda Science Foundation to Proteo-Science Center","JSPS KAKENHI","SPS KAKENHI","Japan Foundation for Applied Enzymology, Research Grant of the Princess Takamatsu Cancer Research Fund, The Research Foundation for Pharmaceutical Sciences"],"pagination":["e202101095"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8321701"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(9)"],"pubmed_abstract":["Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) phosphorylation drives HER2-positive breast cancer cell proliferation. Enforced activation of phosphatases for those receptors could be a therapeutic option for HER2-positive breast cancers. Here, we report that degradation of an endosomal small GTPase, RhoB, by the ubiquitin ligase complex cullin-3 (CUL3)/KCTD10 is essential for both EGFR and HER2 phosphorylation in HER2-positive breast cancer cells. Using human protein arrays produced in a wheat cell-free protein synthesis system, RhoB-GTP, and protein tyrosine phosphatase receptor type H (PTPRH) were identified as interacting proteins of connector enhancer of kinase suppressor of Ras1 (CNKSR1). Mechanistically, constitutive degradation of RhoB, which is mediated by the CUL3"],"journal":["Life science alliance"],"pubmed_title":["CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP."],"pmcid":["PMC8321701"],"funding_grant_id":["19K18030","19K18029","21H02763"],"pubmed_authors":["Higashiyama S","Nakayama J","Takada Y","Kiyoi T","Nakagita T","Nishiyama K","Murakami A","Kamei Y","Chosei M","Maekawa M","Takeda H"],"additional_accession":[]},"is_claimable":false,"name":"CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.","description":"Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) phosphorylation drives HER2-positive breast cancer cell proliferation. Enforced activation of phosphatases for those receptors could be a therapeutic option for HER2-positive breast cancers. Here, we report that degradation of an endosomal small GTPase, RhoB, by the ubiquitin ligase complex cullin-3 (CUL3)/KCTD10 is essential for both EGFR and HER2 phosphorylation in HER2-positive breast cancer cells. Using human protein arrays produced in a wheat cell-free protein synthesis system, RhoB-GTP, and protein tyrosine phosphatase receptor type H (PTPRH) were identified as interacting proteins of connector enhancer of kinase suppressor of Ras1 (CNKSR1). Mechanistically, constitutive degradation of RhoB, which is mediated by the CUL3","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-05-08T13:04:32.231Z","creation":"2022-02-11T04:14:29.304Z"},"accession":"S-EPMC8321701","cross_references":{"pubmed":["34187934"],"doi":["10.26508/lsa.202101095"]}}