Acetylation Versus Ubiquitination

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Science's STKE  25 Mar 2003:
Vol. 2003, Issue 175, pp. tw117-TW117
DOI: 10.1126/stke.2003.175.tw117

Posttranslational modification of lysine residues is an important regulatory mechanism controlling protein activity and stability. Giandomenico et al. report that the activity of transcription factors of the sterol regulatory element binding protein (SREBP) family is increased by acetylation of a residue that can also be the target for ubiquitin conjugation, which promotes proteasome-mediated degradation. The histone acetylase and transcriptional cofactors p300 and CBP interacted with SREBP1 and 2 and acetylated these proteins in vitro and in vivo. The major residue acetylated, based on mutational analysis of SREBP1, was K333 in the DNA binding domain; however, acetylation did not inhibit DNA binding. Mutation of K333 decreased both acetylation and ubiquitination of SREBP1. In vitro, acetylation decreased ubiquitination of SREBP1, suggesting that this lysine may be the target for both types of posttranslational modifications. Coexpression of p300 with SREBP1 yielded increased levels of SREBP1, and expression of a K333Q mutant showed increased cholesterol synthesis activity compared to expression of wild-type SREBP in transfected cells. Thus, acetylation and ubiquitination may be competing reactions controlling the stability and activity of transcription factors, such as SREBPs.

V. Giandomenico, M. Simonsson, E. Grönroos, J. Ericsson, Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors. Mol. Cell. Biol. 23, 2587-2599 (2003). [Abstract] [Full Text]