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Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.

TitleHistone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.
Publication TypeJournal Article
Year of Publication2012
AuthorsEne CI, Edwards L, Riddick G, Baysan M, Woolard K, Kotliarova S, Lai C, Belova G, Cam M, Walling J, Zhou M, Stevenson H, Kim HSug, Killian K, Veenstra T, Bailey R, Song H, Zhang W, Fine HA
JournalPLoS One
Volume7
Issue12
Paginatione51407
Date Published2012
ISSN1932-6203
KeywordsAnimals, Blotting, Western, Cell Differentiation, Cell Transformation, Neoplastic, DNA Primers, Glioblastoma, Histones, Humans, Immunohistochemistry, Immunoprecipitation, Jumonji Domain-Containing Histone Demethylases, Luciferases, Mass Spectrometry, Mice, Mice, SCID, Neoplastic Stem Cells, Protein Stability, Real-Time Polymerase Chain Reaction, Tumor Suppressor Protein p53
Abstract

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.

DOI10.1371/journal.pone.0051407
Alternate JournalPLoS ONE
PubMed ID23236496
PubMed Central IDPMC3517524
Grant List / / Howard Hughes Medical Institute / United States