p63 and p73 are required for p53-dependent apoptosis in response to DNA damage.

Abstract:

:The tumour-suppressor gene p53 is frequently mutated in human cancers and is important in the cellular response to DNA damage. Although the p53 family members p63 and p73 are structurally related to p53, they have not been directly linked to tumour suppression, although they have been implicated in apoptosis. Given the similarity between this family of genes and the ability of p63 and p73 to transactivate p53 target genes, we explore here their role in DNA damage-induced apoptosis. Mouse embryo fibroblasts deficient for one or a combination of p53 family members were sensitized to undergo apoptosis through the expression of the adenovirus E1A oncogene. While using the E1A system facilitated our ability to perform biochemical analyses, we also examined the functions of p63 and p73 using an in vivo system in which apoptosis has been shown to be dependent on p53. Using both systems, we show here that the combined loss of p63 and p73 results in the failure of cells containing functional p53 to undergo apoptosis in response to DNA damage.

journal_name

Nature

journal_title

Nature

authors

Flores ER,Tsai KY,Crowley D,Sengupta S,Yang A,McKeon F,Jacks T

doi

10.1038/416560a

keywords:

subject

Has Abstract

pub_date

2002-04-04 00:00:00

pages

560-4

issue

6880

eissn

0028-0836

issn

1476-4687

pii

416560a

journal_volume

416

pub_type

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