| Literature DB >> 26990986 |
T Van Nguyen1, J Eugene Lee2, Michael J Sweredoski3, Seung-Joo Yang4, Seung-Je Jeon4, Joseph S Harrison5, Jung-Hyuk Yim6, Sang Ghil Lee7, Hiroshi Handa8, Brian Kuhlman5, Ji-Seon Jeong6, Justin M Reitsma1, Chul-Seung Park4, Sonja Hess3, Raymond J Deshaies9.
Abstract
Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4(CRBN) that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.Entities:
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Year: 2016 PMID： 26990986 PMCID： PMC4889030 DOI： 10.1016/j.molcel.2016.02.032
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970