{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nan L"],"funding":["NHLBI NIH HHS","NIGMS NIH HHS"],"pagination":["33116"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5015047"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6"],"pubmed_abstract":["Transforming growth factor β-1 (TGFβ-1)-induced phosphorylation of transcription factors Smad2 and Smad3 plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the molecular regulation of Smad2/Smad3 proteins stability remains a mystery. Here, we show that ubiquitin carboxyl-terminal hydrolase-L5 (UCHL5 or UCH37) de-ubiquitinates both Smad2 and Smad3, up-regulates their stability, and promotes TGFβ-1-induced expression of profibrotic proteins, such as fibronectin (FN) and α-smooth muscle actin (α-SMA). Inhibition or down-regulation of UCHL5 reduced Smad2/Smad3 levels and TGFβ-1-induced the expression of FN and α-SMA in human lung fibroblast. We demonstrate that Smad2 and Smad3 ubiquitination was diminished by over-expression of UCHL5, while it was enhance"],"journal":["Scientific reports"],"pubmed_title":["Ubiquitin carboxyl-terminal hydrolase-L5 promotes TGFβ-1 signaling by de-ubiquitinating and stabilizing Smad2/Smad3 in pulmonary fibrosis."],"pmcid":["PMC5015047"],"funding_grant_id":["R01 HL091916","R01 GM115389","R01 HL112791","R01 HL126990","P01 HL114453"],"pubmed_authors":["Kass DJ","Jacko AM","Tan J","Wang D","Ma H","Zhao J","Zhao Y","Nan L"],"additional_accession":[]},"is_claimable":false,"name":"Ubiquitin carboxyl-terminal hydrolase-L5 promotes TGFβ-1 signaling by de-ubiquitinating and stabilizing Smad2/Smad3 in pulmonary fibrosis.","description":"Transforming growth factor β-1 (TGFβ-1)-induced phosphorylation of transcription factors Smad2 and Smad3 plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the molecular regulation of Smad2/Smad3 proteins stability remains a mystery. Here, we show that ubiquitin carboxyl-terminal hydrolase-L5 (UCHL5 or UCH37) de-ubiquitinates both Smad2 and Smad3, up-regulates their stability, and promotes TGFβ-1-induced expression of profibrotic proteins, such as fibronectin (FN) and α-smooth muscle actin (α-SMA). Inhibition or down-regulation of UCHL5 reduced Smad2/Smad3 levels and TGFβ-1-induced the expression of FN and α-SMA in human lung fibroblast. We demonstrate that Smad2 and Smad3 ubiquitination was diminished by over-expression of UCHL5, while it was enhance","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Sep","modification":"2025-04-05T10:43:20.023Z","creation":"2019-03-27T02:23:45Z"},"accession":"S-EPMC5015047","cross_references":{"pubmed":["27604640"],"doi":["10.1038/srep33116"]}}