title: Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response.
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.
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors: Yung-Lin
authors: YL
authors: Hsieh
authors: Hong-Yi
authors: HY
authors: Kuo
authors: Che-Chang
authors: CC
authors: Chang
authors: Mandar T
authors: MT
authors: Naik
authors: Pei-Hsin
authors: PH
authors: Liao
authors: Chun-Chen
authors: CC
authors: Ho
authors: Tien-Chi
authors: TC
authors: Huang
authors: Jen-Chong
authors: JC
authors: Jeng
authors: Pang-Hung
authors: PH
authors: Hsu
authors: Ming-Daw
authors: MD
authors: Tsai
authors: Tai-Huang
authors: TH
authors: Huang
authors: Hsiu-Ming
authors: HM
authors: Shih
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism* / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D025842:SUMO-1 Protein / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism / Q000502:physiology; D058207:Sumoylation / Q000187:drug effects / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D050807:ets-Domain Protein Elk-1; D000123:Acetyltransferases; D044763:Ubiquitin-Conjugating Enzymes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000098843:Ubiquitin-Conjugating Enzyme UBC9
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