Characterization of a novel interaction between JMJD2a and p53 (2014)

Undergraduates: Hanjia Guo, Scott B. Rothbart, PhD., Erin K. Shanle, PhD

Faculty Advisor: Brian Strahl
Department: Chemistry

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Histone post-translational modifications (PTMs) are critical to many essential biological processes, including gene transcription and DNA repair, by altering the physical structure of chromatin and serving as docking sites for reader proteins. JMJD2a is a unique protein with the ability to both erase and read histone PTMs. It has been shown that as a histone demethylase, JMJD2a removes di- and tri-methylation from lysines 9 and 36 on the histone H3 tail (H3K9me2/3 and H3K36me2/3). As a reader, JMJD2a binds tri-methylated lysine 4 on the histone H3 tail (H3K4me3) and di- and tri-methylated lysine 20 on the histone H4 tail (H4K20me2/3) through its double Tudor domain (dTd). In this presentation, I will show the tumor suppressor p53 as the first non-histone target of JMJD2a. When cellular processes malfunction, p53 levels within the cell increase exponentially and initiate a multitude of regulatory pathways, including apoptosis. In 50 percent of all cancers, p53 is either mutated or deleted. Peptide micro-array, in-solution peptide pulldown, and protein-peptide immunoprecipitation all suggest that the JMJD2a, via its dTd, binds p53 at di-methylated lysine 382 (p53K382me2), a mark that increases upon DNA damage. This novel interaction implicates the demethylase JMJD2a in p53 biology.