PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function
Keskin, Nazlı and Deniz, Emre and Eryılmaz, Jitka and Ün, Manolya and Altınuşak, Tuğçe and Erşahin, Tülin and Atalay, Rengül Çetin and Sakaguchi, Shinya and Ellmeier, Wilfried and Erman, Batu (2015) PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function. Molecular and Cellular Biology, 35 (10). pp. 1741-1753. ISSN 0270-7306 (Print) 1098-5549 (Online)
Official URL: http://dx.doi.org/10.1128/MCB.01475-14
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 tran- scriptional 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 bind- ing. This study documents PATZ1 as a novel player in the p53 pathway.
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