{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Camp ND"],"funding":["Howard Hughes Medical Institute","NHLBI NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["6539-50"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3307315"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["287(9)"],"pubmed_abstract":["WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the β-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor β-catenin, a key control point in the WNT/β-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of β-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein."],"pmcid":["PMC3307315"],"funding_grant_id":["R01 CA107134","R00 HL103768","T32 GM07270","T32 GM007270"],"pubmed_authors":["Davison JM","Zheng N","Major MB","James RG","Moon RT","Dawson DW","Houck SA","Camp ND","Yan F","Tang X"],"additional_accession":[]},"is_claimable":false,"name":"Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein.","description":"WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the β-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor β-catenin, a key control point in the WNT/β-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of β-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Feb","modification":"2025-04-18T13:57:42.542Z","creation":"2019-03-27T00:51:21Z"},"accession":"S-EPMC3307315","cross_references":{"pubmed":["22215675"],"doi":["10.1074/jbc.M111.316471"]}}