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

Molecular and Cellular Biology
Nazli KeskinBatu Erman

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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Citations

Jun 15, 2016·Biochemical and Biophysical Research Communications·Ren-An ChenYing-Min Liang
Apr 30, 2016·Scientific Reports·Michela VitielloMonica Fedele
Jun 5, 2020·Acta Crystallographica. Section D, Structural Biology·Sofia PiepoliBatu Erman
Feb 19, 2021·Frontiers in Cell and Developmental Biology·Zhen Long NgQiang Wu
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Sara MancinelliMonica Fedele

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