{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yuan B"],"funding":["Natural Science Foundation of Zhejiang Province","China Postdoctoral Science Foundation","National Natural Science Foundation of China"],"pagination":["e111549"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9929636"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["42(4)"],"pubmed_abstract":["YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCF<sup>β-TrCP</sup> . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to β-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer."],"journal":["The EMBO journal"],"pubmed_title":["HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity."],"pmcid":["PMC9929636"],"funding_grant_id":["2020M671701","31730057","LD21C070001","91940302","32200568"],"pubmed_authors":["Shen L","Liang T","Liu J","Xu P","Zhu Y","Zhao B","Cao J","Luo H","Qiu Y","Feng XH","Cao X","Yuan B","Shi A","Zhang C","Shi J","Yu Y"],"additional_accession":[]},"is_claimable":false,"name":"HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.","description":"YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCF<sup>β-TrCP</sup> . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to β-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-04T12:06:06.41Z","creation":"2025-04-04T12:06:06.41Z"},"accession":"S-EPMC9929636","cross_references":{"pubmed":["36598329"],"doi":["10.15252/embj.2022111549"]}}