{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Herhaus L"],"funding":["Medical Research Council"],"pagination":["140065"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4042855"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(5)"],"pubmed_abstract":["Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, "],"journal":["Open biology"],"pubmed_title":["USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling."],"pmcid":["PMC4042855"],"funding_grant_id":["U117597140","MC_U127092717","MC_U117597140","MC_UU_12016/3"],"pubmed_authors":["Cummins TD","Sapkota GP","Wasmus L","Ewan R","Bruce D","Herhaus L","Vogt J","Al-Salihi MA","Dingwell KS","Macartney T","Smith JC","Weidlich S"],"additional_accession":[]},"is_claimable":false,"name":"USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling.","description":"Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, ","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 May","modification":"2025-04-21T20:06:07.671Z","creation":"2019-03-27T01:29:22Z"},"accession":"S-EPMC4042855","cross_references":{"pubmed":["24850914"],"doi":["10.1098/rsob.140065"]}}