PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function

Date
2015
Authors
Keskin, N.
Deniz, E.
Eryilmaz J.
Un, M.
Batur, T.
Ersahin, T.
Atalay, R.C.
Sakaguchi, S.
Ellmeier W.
Erman, B.
Advisor
Supervisor
Co-Advisor
Co-Supervisor
Instructor
Source Title
Molecular and Cellular Biology
Print ISSN
0270-7306
Electronic ISSN
Publisher
American Society for Microbiology
Volume
35
Issue
10
Pages
1741 - 1753
Language
English
Type
Article
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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. © 2015, American Society for Microbiology.

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Keywords
doxorubicin, heterodimer, protein p53, transcription factor, transcription factor patz1, unclassified drug, animal cell, Article, carboxy terminal sequence, cell adhesion, cell growth, DNA damage, down regulation, embryo, gene ontology, human, human cell, morphogenesis, mouse, nonhuman, priority journal, protein binding, protein domain, protein expression, protein function, protein interaction, RNA sequence, transcription initiation
Citation
Published Version (Please cite this version)