GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA.

Abstract:

:The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism Murr1 Domain 1 (COMMD1) and Cul2. We report here that GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses kappaB-dependent transcription. In this role, the acetyltransferase activity of GCN5 is not required. Interestingly, GCN5 binds more avidly to RelA after phosphorylation on Ser 468, an event that is dependent on IKK activity. Consistent with this, we find that both GCN5 and the IkappaB Kinase (IKK) complex promote RelA degradation. Collectively, the data indicate that GCN5 participates in the ubiquitination process as an accessory factor for a ubiquitin ligase, where it provides a novel link between phosphorylation and ubiquitination.

journal_name

Genes Dev

journal_title

Genes & development

authors

Mao X,Gluck N,Li D,Maine GN,Li H,Zaidi IW,Repaka A,Mayo MW,Burstein E

doi

10.1101/gad.1748409

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

849-61

issue

7

eissn

0890-9369

issn

1549-5477

pii

23/7/849

journal_volume

23

pub_type

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