{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Segarra-Fas A"],"funding":["Medical Research Council","Wellcome Trust","NIGMS NIH HHS"],"pagination":["eabm5995"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7613676"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(742)"],"pubmed_abstract":["The E3 ubiquitin ligase RNF12 plays essential roles during development, and the gene encoding it, <i>RLIM</i>, is mutated in the X-linked human developmental disorder Tonne-Kalscheuer syndrome (TOKAS). Substrates of RNF12 include transcriptional regulators such as the pluripotency-associated transcriptional repressor REX1. Using global quantitative proteomics in male mouse embryonic stem cells, we identified the deubiquitylase USP26 as a putative downstream target of RNF12 activity. RNF12 relieved REX1-mediated repression of <i>Usp26</i>, leading to an increase in USP26 abundance and the formation of RNF12-USP26 complexes. Interaction with USP26 prevented RNF12 autoubiquitylation and proteasomal degradation, thereby establishing a transcriptional feed-forward loop that amplified RNF12-depe"],"journal":["Science signaling"],"pubmed_title":["An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations."],"pmcid":["PMC7613676"],"funding_grant_id":["211209","MR/N000609/1","211209/Z/18/Z","R01 GM128168"],"pubmed_authors":["Espejo-Serrano C","Bustos F","Segarra-Fas A","Toth R","Bach I","Wang F","Nardocci G","Findlay GM","Zhou H","Macartney T"],"additional_accession":[]},"is_claimable":false,"name":"An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations.","description":"The E3 ubiquitin ligase RNF12 plays essential roles during development, and the gene encoding it, <i>RLIM</i>, is mutated in the X-linked human developmental disorder Tonne-Kalscheuer syndrome (TOKAS). Substrates of RNF12 include transcriptional regulators such as the pluripotency-associated transcriptional repressor REX1. Using global quantitative proteomics in male mouse embryonic stem cells, we identified the deubiquitylase USP26 as a putative downstream target of RNF12 activity. RNF12 relieved REX1-mediated repression of <i>Usp26</i>, leading to an increase in USP26 abundance and the formation of RNF12-USP26 complexes. Interaction with USP26 prevented RNF12 autoubiquitylation and proteasomal degradation, thereby establishing a transcriptional feed-forward loop that amplified RNF12-depe","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-07-14T16:07:59.871Z","creation":"2024-10-18T02:25:23.994Z"},"accession":"S-EPMC7613676","cross_references":{"pubmed":["35857630"],"doi":["10.1126/scisignal.abm5995"]}}