Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response

Yung Lin Hsieh, Hong Yi Kuo, Che Chang Chang, Mandar T. Naik, Pei Hsin Liao, Chun Chen Ho, Tien Chi Huang, Jen Chong Jeng, Pang Hung Hsu, Ming Daw Tsai, Tai Huang Huang, Hsiu Ming Shih

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39 Citations (Scopus)

Abstract

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 ψ-K-X-E/D consensus motif, such as CBP and Elk-1, but not substrates with core ψ-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.

Original languageEnglish
Pages (from-to)791-804
Number of pages14
JournalEMBO Journal
Volume32
Issue number6
DOIs
Publication statusPublished - 2013 Mar 20

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Keywords

  • SIRT1
  • Ubc9
  • acetylation
  • hypoxia
  • sumoylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Hsieh, Y. L., Kuo, H. Y., Chang, C. C., Naik, M. T., Liao, P. H., Ho, C. C., Huang, T. C., Jeng, J. C., Hsu, P. H., Tsai, M. D., Huang, T. H., & Shih, H. M. (2013). Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response. EMBO Journal, 32(6), 791-804. https://doi.org/10.1038/emboj.2013.5