dc.contributor.author | Garcia-Garcia, Juncal | |
dc.contributor.author | Overå, Katrine Stange | |
dc.contributor.author | Khan, Waqas | |
dc.contributor.author | Sjøttem, Eva | |
dc.date.accessioned | 2022-03-02T12:55:46Z | |
dc.date.available | 2022-03-02T12:55:46Z | |
dc.date.issued | 2021-05-17 | |
dc.description.abstract | TRIM32 is an E3 ligase implicated in diverse biological pathways and pathologies such as muscular dystrophy and cancer. TRIM32 are expressed both as full-length proteins, and as a truncated protein. The mechanisms for regulating these isoforms are poorly understood. Here we identify a PEST sequence in TRIM32 located in the unstructured region between the RING-BBox-CoiledCoil domains and the NHL repeats. The PEST sequence directs cleavage of TRIM32, generating a truncated protein similarly to the short isoform. We map three lysine residues that regulate PEST mediated cleavage and auto-ubiquitylation activity of TRIM32. Mimicking acetylation of lysine K247 completely inhibits TRIM32 cleavage, while the lysines K50 and K401 are implicated in auto-ubiquitylation activity. We show that the short isoform of TRIM32 is catalytic inactive, suggesting a dominant negative role. These findings uncover that TRIM32 is regulated by post-translational modifications of three lysine residues, and a conserved PEST sequence. | en_US |
dc.identifier.citation | Garcia-Garcia J, Overå KS, Khan W, Sjøttem E. Generation of the short TRIM32 isoform is regulated by Lys 247 acetylation and a PEST sequence. PLOS ONE. 2021 | en_US |
dc.identifier.cristinID | FRIDAID 1982339 | |
dc.identifier.doi | 10.1371/journal.pone.0251279 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://hdl.handle.net/10037/24226 | |
dc.language.iso | eng | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.journal | PLOS ONE | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
dc.title | Generation of the short TRIM32 isoform is regulated by Lys 247 acetylation and a PEST sequence | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |