Journal
EMBO JOURNAL
Volume 32, Issue 6, Pages 791-804Publisher
WILEY
DOI: 10.1038/emboj.2013.5
Keywords
acetylation; hypoxia; SIRT1; sumoylation; Ubc9
Categories
Funding
- National Science Council [NSC101-2321-B-001-029, NSC100-2321-B-001-004, NSC100-3112-B-001-004]
- Academia Sinica Investigator Award
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While numerous small ubiquitin-like modifier (SUMO) conjugated substrates have been identified, very little is known about the cellular signalling mechanisms that differentially regulate substrate sumoylation. Here, we show that acetylation of SUMO E2 conjugase Ubc9 selectively downregulates the sumoylation of substrates with negatively charged amino acid-dependent sumoylation motif (NDSM) consisting of clustered acidic residues located downstream from the core psi-K-X-E/D consensus motif, such as CBP and Elk-1, but not substrates with core psi-K-X-E/D motif alone or SUMO-interacting motif. Ubc9 is acetylated at residue K65 and K65 acetylation attenuates Ubc9 binding to NDSM substrates, causing a reduction in NDSM substrate sumoylation. Furthermore, Ubc9 K65 acetylation can be downregulated by hypoxia via SIRT1, and is correlated with hypoxia-elicited modulation of sumoylation and target gene expression of CBP and Elk-1 and cell survival. Our data suggest that Ubc9 acetylation/deacetylation serves as a dynamic switch for NDSM substrate sumoylation and we report a previously undescribed SIRT1/Ubc9 regulatory axis in the modulation of protein sumoylation and the hypoxia response. The EMBO Journal (2013) 32, 791-804. doi:10.1038/emboj.2013.5; Published online 8 February 2013
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