NDLI: TAp63γ Demethylation Regulates Protein Stability and Cellular Distribution during Neural Stem Cell Differentiation

Content Provider	PubMed Central
Author	Fonseca, Maria B. Nunes, Ana F. Morgado, Ana L. Susana, SolÃ¡ Rodrigues, CecÃlia M. P.
Editor	Mantovani, Roberto
Copyright Year	2012
Abstract	p63 is a close relative of the p53 tumor suppressor and transcription factor that modulates cell fate. The full-length isoform of p63, containing a transactivation (TA) domain (TAp63) is an essential proapoptotic protein in neural development. The role of p63 in epithelial development is also well established; however, its precise function during neural differentiation remains largely controversial. Recently, it has been demonstrated that several conserved elements of apoptosis are also integral components of cellular differentiation; p53 directly interacts with key regulators of neurogenesis. The aim of this study was to evaluate the role of p63 during mouse neural stem cell (NSC) differentiation and test whether the histone H3 lysine 27-specific demethylase JMJD3 interacts with p63 to redirect NSCs to neurogenesis. Our results showed that JMJD3 and TAp63γ are coordinately regulated to establish neural-specific gene expression programs in NSCs undergoing differentiation. JMJD3 overexpression increased TAp63γ levels in a demethylase activity-dependent manner. Importantly, overexpression of TAp63γ increased β-III tubulin whereas downregulation of TAp63γ by specific p63 siRNA decreased β-III tubulin. Immunoprecipitation assays demonstrated direct interaction between TAp63γ and JMJD3, and modulation of TAp63γ methylation status by JMJD3-demethylase activity. Importantly, the demethylase activity of JMJD3 influenced TAp63γ protein stabilization and cellular distribution, as well as TAp63γ-regulated neurogenesis. These findings clarify the role of p63 in adult neural progenitor cells and reveal TAp63γ as a direct target for JMJD3-mediated neuronal commitment.
Related Links	http://dx.doi.org/10.1371/journal.pone.0052417
Starting Page	52417
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-12-14
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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