1. Regulation of NUB1 Activity through Non- Proteolytic Mdm2-Mediated Ubiquitination
- Author
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Bonacci, Thomas, Audebert, Stéphane, Camoin, Luc, Baudelet, Emilie, Iovanna, Juan-Lucio, Soubeyran, Philippe, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Bidaut, Ghislain
- Subjects
NEDD8 Protein ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Research and Analysis Methods ,Arginine ,Biochemistry ,Ligases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Immunoprecipitation ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Post-Translational Modification ,Amino Acids ,Protein Interactions ,lcsh:Science ,Imidazole ,Ubiquitins ,Adaptor Proteins, Signal Transducing ,Huntingtin Protein ,Organic Compounds ,Lysine ,Organic Chemistry ,lcsh:R ,Ubiquitination ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Proto-Oncogene Proteins c-mdm2 ,Ubiquitin Ligases ,Precipitation Techniques ,Enzymes ,[SDV] Life Sciences [q-bio] ,Chemistry ,HEK293 Cells ,Physical Sciences ,Enzymology ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,lcsh:Q ,Basic Amino Acids ,Research Article ,Transcription Factors - Abstract
International audience; NUB1 (Nedd8 ultimate buster 1) is an adaptor protein which negatively regulates the ubiqui-tin-like protein Nedd8 as well as neddylated proteins levels through proteasomal degradation. However, molecular mechanisms underlying this function are not completely understood. Here, we report that the oncogenic E3 ubiquitin ligase Mdm2 is a new NUB1 interacting protein which induces its ubiquitination. Interestingly, we found that Mdm2-mediated ubiquitination of NUB1 is not a proteolytic signal. Instead of promoting the conjugation of polyubiquitin chains and the subsequent proteasomal degradation of NUB1, Mdm2 rather induces its di-ubiquitination on lysine 159. Importantly, mutation of lysine 159 into arginine inhibits NUB1 activity by impairing its negative regulation of Nedd8 and of neddylated proteins. We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159.
- Published
- 2017