%0 Journal Article
%T Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization
%A Chibawanye I. Ene
%A Lincoln Edwards
%A Gregory Riddick
%A Mehmet Baysan
%A Kevin Woolard
%A Svetlana Kotliarova
%A Chen Lai
%A Galina Belova
%A Maggie Cam
%A Jennifer Walling
%A Ming Zhou
%A Holly Stevenson
%A Hong Sug Kim
%A Keith Killian
%A Timothy Veenstra
%A Rolanda Bailey
%A Hua Song
%A Wei Zhang
%A Howard A. Fine
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0051407
%X Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0051407