title: PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.
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.
authors.affiliation: 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.
authors.forename: Nazli
authors.initials: N
authors.lastname: Keskin
authors.affiliation: 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.
authors.forename: Emre
authors.initials: E
authors.lastname: Deniz
authors.affiliation: Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
authors.forename: Jitka
authors.initials: J
authors.lastname: Eryilmaz
authors.affiliation: Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
authors.forename: Manolya
authors.initials: M
authors.lastname: Un
authors.affiliation: Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
authors.forename: Tugce
authors.initials: T
authors.lastname: Batur
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey Informatics Institute, Middle East Technical University, Ankara, Turkey.
authors.forename: Tulin
authors.initials: T
authors.lastname: Ersahin
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey Informatics Institute, Middle East Technical University, Ankara, Turkey.
authors.forename: Rengul
authors.initials: R
authors.lastname: Cetin Atalay
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
authors.affiliation: 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.
authors.forename: Batu
authors.initials: B
authors.lastname: Erman
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair; D004317:Doxorubicin / Q000494:pharmacology; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D051741:Kruppel-Like Transcription Factors; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; C412784:PATZ1 protein, human; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C485875:Zfp278 protein, mouse; D004317:Doxorubicin