| Literature DB >> 26748827 |
Magdalena Wienken1, Antje Dickmanns1, Alice Nemajerova2, Daniela Kramer1, Zeynab Najafova3, Miriam Weiss1, Oleksandra Karpiuk1, Moustapha Kassem4, Yanping Zhang5, Guillermina Lozano6, Steven A Johnsen3, Ute M Moll7, Xin Zhang8, Matthias Dobbelstein9.
Abstract
The MDM2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that MDM2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, MDM2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the MDM2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. MDM2 physically associated with EZH2 on chromatin, enhancing the trimethylation of histone 3 at lysine 27 and the ubiquitination of histone 2A at lysine 119 (H2AK119) at its target genes. Removing MDM2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, MDM2 supports the Polycomb-mediated repression of lineage-specific genes, independent of p53.Entities:
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Year: 2015 PMID： 26748827 PMCID： PMC6284523 DOI： 10.1016/j.molcel.2015.12.008
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970