A molecular basis for phosphorylation-dependent SUMO conjugation by the E2 UBC9 Journal Article
| Authors: | Mohideen, M. F.; Capili, A. D.; Bilimoria, P. M.; Yamada, T.; Bonni, A.; Lima, C. D. |
| Article Title: | A molecular basis for phosphorylation-dependent SUMO conjugation by the E2 UBC9 |
| Abstract: | Phosphorylation and small ubiquitin-like modifier (SUMO) conjugation contribute to the spatial and temporal regulation of substrates containing phosphorylation-dependent SUMO consensus motifs (PDSMs). Myocyte-enhancement factor 2 (MEF2) is a transcription factor and PDSM substrate whose modification by SUMO drives postsynaptic dendritic differentiation. NMR analysis revealed that the human SUMO E2 interacted with model substrates for phosphorylated and nonphosphorylated MEF2 in similar extended conformations. Mutational and biochemical analysis identified a basic E2 surface that enhanced SUMO conjugation to phosphorylated PDSM substrates MEF2 and heat-shock transcription factor 1 (HSF1), but not to nonphosphorylated MEF2 or HSF1, nor the non-PDSM substrate p53. Mutant ubiquitin-conjugating enzyme UBC9 isoforms defective in promoting SUMO conjugation to phosphorylated MEF2 in vitro and in vivo also impair postsynaptic differentiation in organotypic cerebellar slices. These data support an E2-dependent mechanism that underlies phosphorylation-dependent SUMO conjugation in pathways that range from the heat-shock response to nuclear hormone signaling to brain development. © 2009 Nature America, Inc. All rights reserved. |
| Keywords: | signal transduction; protein phosphorylation; gene mutation; protein analysis; animals; cerebellum; cell line; protein binding; in vivo study; in vitro study; phosphorylation; protein p53; molecular sequence data; sequence alignment; substrate specificity; models, molecular; protein structure, tertiary; rats; sumo protein; ubiquitin-conjugating enzymes; nuclear magnetic resonance; amino acid motifs; heat shock transcription factor 1; myocyte enhancer factor 2; dendrite; biocatalysis; dendrites; mads domain proteins; small ubiquitin-related modifier proteins |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 16 |
| Issue: | 9 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-09-01 |
| Start Page: | 945 |
| End Page: | 952 |
| Language: | English |
| DOI: | 10.1038/nsmb.1648 |
| PUBMED: | 19684601 |
| PROVIDER: | scopus |
| PMCID: | PMC2771680 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 30 November 2010" - "CODEN: NSMBC" - "Source: Scopus" |
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