Role of Pirh2 in mediating the regulation of p53 and c-Myc.

Abstract:

:Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2(-/-) mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Hakem A,Bohgaki M,Lemmers B,Tai E,Salmena L,Matysiak-Zablocki E,Jung YS,Karaskova J,Kaustov L,Duan S,Madore J,Boutros P,Sheng Y,Chesi M,Bergsagel PL,Perez-Ordonez B,Mes-Masson AM,Penn L,Squire J,Chen X,Jurisica I

doi

10.1371/journal.pgen.1002360

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

e1002360

issue

11

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-11-00625

journal_volume

7

pub_type

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