PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.

Abstract:

:Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq) and real-time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage-inducing drug doxorubicin results in the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53-dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway.

journal_name

Mol Cell Biol

authors

Keskin N,Deniz E,Eryilmaz J,Un M,Batur T,Ersahin T,Cetin Atalay R,Sakaguchi S,Ellmeier W,Erman B

doi

10.1128/MCB.01475-14

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1741-53

issue

10

eissn

0270-7306

issn

1098-5549

pii

MCB.01475-14

journal_volume

35

pub_type

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