Research ArticleBiochemistry

Acetylation-dependent regulation of MDM2 E3 ligase activity dictates its oncogenic function

+ See all authors and affiliations

Sci. Signal.  14 Feb 2017:
Vol. 10, Issue 466,
DOI: 10.1126/scisignal.aai8026

You are currently viewing the editor's summary.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Acetylation directs MDM2 activity

As a tumor suppressor, the transcription factor p53 promotes cell death when cellular and genomic integrity is compromised. The ubiquitin E3 ligase MDM2 marks p53 and itself for degradation and is thus a critical regulatory node controlling cell death and survival. Nihira et al. explored what dictated autoubiquitination versus p53-targeted activity by MDM2 and found that acetylation at two lysine residues in its nuclear localization sequence changed intermolecular interactions. When acetylated, an increased interaction with a deubiquitinase stabilized this E3 ubiquitin ligase and enabled greater activity toward p53. Deacetylation of these sites in response to genotoxic stress promoted more MDM2 autoubiquitination, thereby increasing p53 stability and promoting cell death. Thus, acetylation in this motif of MDM2 contributes to the cell’s decision between survival and death.

Related Content