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

Date

2015-05-01

Author

Keskin, Nazli
Deniz, Emre
Eryilmaz, Jitka
Un, Manolya
Batur, Tugce
Ersahin, Tulin
Atalay, Rengül
Sakaguchi, Shinya
Ellmeier, Wilfried
ERMAN, MEHMET BATU

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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.

Subject Keywords

Finger protein mazr, Helper-free, High-titer, At-hook, Gene, Domain, Methylation, Recognition, Expression, 53bp1

URI

https://hdl.handle.net/11511/30740

Journal

MOLECULAR AND CELLULAR BIOLOGY

DOI

https://doi.org/10.1128/mcb.01475-14

Collections

Graduate School of Informatics, Article

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Citation Formats

N. Keskin et al., “PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function,” MOLECULAR AND CELLULAR BIOLOGY, pp. 1741–1753, 2015, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30740.