PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function

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dc.citation.epage1753en_US
dc.citation.issueNumber10en_US
dc.citation.spage1741en_US
dc.citation.volumeNumber35en_US
dc.contributor.authorKeskin, N.en_US
dc.contributor.authorDeniz, E.en_US
dc.contributor.authorEryilmaz J.en_US
dc.contributor.authorUn, M.en_US
dc.contributor.authorBatur, T.en_US
dc.contributor.authorErsahin, T.en_US
dc.contributor.authorAtalay, R.C.en_US
dc.contributor.authorSakaguchi, S.en_US
dc.contributor.authorEllmeier W.en_US
dc.contributor.authorErman, B.en_US
dc.date.accessioned2016-02-08T10:03:39Z
dc.date.available2016-02-08T10:03:39Z
dc.date.issued2015en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractInsults 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. © 2015, American Society for Microbiology.en_US
dc.description.provenanceMade available in DSpace on 2016-02-08T10:03:39Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 70227 bytes, checksum: 26e812c6f5156f83f0e77b261a471b5a (MD5) Previous issue date: 2015en
dc.identifier.doi10.1128/MCB.01475-14en_US
dc.identifier.issn0270-7306
dc.identifier.urihttp://hdl.handle.net/11693/22703
dc.language.isoEnglishen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1128/MCB.01475-14en_US
dc.source.titleMolecular and Cellular Biologyen_US
dc.subjectdoxorubicinen_US
dc.subjectheterodimeren_US
dc.subjectprotein p53en_US
dc.subjecttranscription factoren_US
dc.subjecttranscription factor patz1en_US
dc.subjectunclassified drugen_US
dc.subjectanimal cellen_US
dc.subjectArticleen_US
dc.subjectcarboxy terminal sequenceen_US
dc.subjectcell adhesionen_US
dc.subjectcell growthen_US
dc.subjectDNA damageen_US
dc.subjectdown regulationen_US
dc.subjectembryoen_US
dc.subjectgene ontologyen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectmorphogenesisen_US
dc.subjectmouseen_US
dc.subjectnonhumanen_US
dc.subjectpriority journalen_US
dc.subjectprotein bindingen_US
dc.subjectprotein domainen_US
dc.subjectprotein expressionen_US
dc.subjectprotein functionen_US
dc.subjectprotein interactionen_US
dc.subjectRNA sequenceen_US
dc.subjecttranscription initiationen_US
dc.titlePATZ1 is a DNA damage-responsive transcription factor that inhibits p53 functionen_US
dc.typeArticleen_US

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