PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function
Author
Keskin, N.
Deniz, E.
Eryilmaz J.
Un, M.
Batur, T.
Ersahin, T.
Atalay, R.C.
Sakaguchi, S.
Ellmeier W.
Erman, B.
Date
2015Source Title
Molecular and Cellular Biology
Print ISSN
0270-7306
Publisher
American Society for Microbiology
Volume
35
Issue
10
Pages
1741 - 1753
Language
English
Type
ArticleItem Usage Stats
118
views
views
119
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downloads
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.
Keywords
doxorubicinheterodimer
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
Permalink
http://hdl.handle.net/11693/22703Published Version (Please cite this version)
http://dx.doi.org/10.1128/MCB.01475-14Collections
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