MSL2 promotes Mdm2-independent cytoplasmic localization of p53.
Although it was originally thought of as a passive way to block the nuclear function of p53, accumulating evidence suggests that cytoplasmic localization of p53 plays an active role in p53-mediated functions such as apoptosis and autophagy. Previous studies by us and others demonstrated that Mdm2-mediated p53 ubiquitination induces both degradation and cytoplasmic localization. Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization.
Kruse
Jan-Philipp
JP
Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Gu
Wei
W
Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032. Electronic address: wg8@columbia.edu.
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
D016159:Tumor Suppressor Protein p53; C539613:MSL2 protein, mouse; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases; D008239:Lysine