SUMO E3 ligase activity of TRIM proteins.
SUMOylation governs numerous cellular processes and is essential to most eukaryotic life. Despite increasing recognition of the importance of this process, an extremely limited number of small ubiquitin-like modifier (SUMO) protein ligases (E3s) have been identified. Here we show that at least some members of the functionally diverse tripartite motif (TRIM) superfamily are SUMO E3s. These TRIM proteins bind both the SUMO-conjugating enzyme Ubc9 and substrates and strongly enhance transfer of SUMOs from Ubc9 to these substrates. Among the substrates of TRIM SUMO E3s are the tumor suppressor p53 and its principal antagonist Mdm2. The E3 activity depends on the TRIM motif, suggesting it to be the first widespread SUMO E3 motif. Given the large number of TRIM proteins, our results may greatly expand the identified SUMO E3s. Furthermore, TRIM E3 activity may be an important contributor to SUMOylation specificity and the versatile functions of TRIM proteins.
Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19096, USA.
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D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D000070584:Tripartite Motif Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D051736:Proto-Oncogene Proteins c-mdm2; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins; C070576:PML protein, human