{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["de Keizer PL"],"funding":["Cancer Research UK"],"pagination":["8526-36"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2989643"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["70(21)"],"pubmed_abstract":["Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAF(V600E) oncogene, which arises commonly in melanoma. BRAF(V600E) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH(2) terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr(223), Ser(226), Thr(447), and Thr(451). BRAF(V600E)-induced FOXO4 phosphorylation resulted in p21(cip1)-mediated cell senescence independ"],"journal":["Cancer research"],"pubmed_title":["Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence."],"pmcid":["PMC2989643"],"funding_grant_id":["A10433","Ref C107/A10433"],"pubmed_authors":["van den Broek NJ","de Keizer PL","Brenkman AB","de Bruin A","Marais R","Burgering BM","Riedl-Polderman PE","Packer LM","Szypowska AA","Dansen TB"],"additional_accession":[]},"is_claimable":false,"name":"Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence.","description":"Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAF(V600E) oncogene, which arises commonly in melanoma. BRAF(V600E) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH(2) terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr(223), Ser(226), Thr(447), and Thr(451). BRAF(V600E)-induced FOXO4 phosphorylation resulted in p21(cip1)-mediated cell senescence independ","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Nov","modification":"2025-04-18T14:38:04.176Z","creation":"2019-03-27T00:36:53Z"},"accession":"S-EPMC2989643","cross_references":{"pubmed":["20959475"],"doi":["10.1158/0008-5472.can-10-1563","10.1158/0008-5472.CAN-10-1563"]}}