2. Academic Validation
  3. PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function

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

  • Mol Cell Biol. 2015 May;35(10):1741-53. doi: 10.1128/MCB.01475-14.
Nazli Keskin 1,  Emre Deniz 1,  Jitka Eryilmaz 2,  Manolya Un 2,  Tugce Batur 2,  Tulin Ersahin 3,  Rengul Cetin Atalay 3,  Shinya Sakaguchi 4,  Wilfried Ellmeier 4,  Batu Erman 5
Affiliations

Affiliations

  • 1 Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey Sabanci University Nanotechnology Research and Application Center-SUNUM, Istanbul, Turkey.
  • 2 Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
  • 3 Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey Informatics Institute, Middle East Technical University, Ankara, Turkey.
  • 4 Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • 5 Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey Sabanci University Nanotechnology Research and Application Center-SUNUM, Istanbul, Turkey batu@sabanciuniv.edu.
PMID: 25755280 DOI: 10.1128/MCB.01475-14
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.

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