PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity

Oncogene
Mario P TschanBruce E Torbett

Abstract

The transcription factor PU.1 is essential for terminal myeloid differentiation, B- and T-cell development, erythropoiesis and hematopoietic stem cell maintenance. PU.1 functions as oncogene in Friend virus-induced erythroleukemia and as tumor suppressor in acute myeloid leukemias. Moreover, Friend virus-induced erythroleukemia requires maintenance of PU.1 expression and the disruption of p53 function greatly accelerates disease progression. It has been hypothesized that p53-mediated expression of the p21(Cip1) cell cycle inhibitor during differentiation of pre-erythroleukemia cells promotes selection against p53 function. In addition to the blockage of erythroblast differentiation provided by increased levels of PU.1, we propose that PU.1 alters p53 function. We demonstrate that PU.1 reduces the transcriptional activity of the p53 tumor suppressor family and thus inhibits activation of genes important for cell cycle regulation and apoptosis. Inhibition is mediated through binding of PU.1 to the DNA-binding and/or oligomerization domains of p53/p73 proteins. Lastly, knocking down endogenous PU.1 in p53 wild-type REH B-cell precursor leukemia cells leads to increased expression of the p53 target p21(Cip1).

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Citations

Apr 28, 2012·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Xiangyu MaWei Zheng
Jul 23, 2011·PloS One·Rukhsana JabeenMark H Kaplan
Aug 23, 2011·PloS One·Haroon NaeemRalf Zimmer
Mar 3, 2010·Seminars in Cancer Biology·Anwesha DeyChandra S Verma
Jul 22, 2014·Leukemia Research·Aladin HaimoviciMario P Tschan
Nov 26, 2010·Molecular Immunology·Jasmin BatlinerMario P Tschan
Apr 1, 2017·Cell Death and Differentiation·Aladin HaimoviciMario P Tschan
Jan 9, 2015·Journal of Leukocyte Biology·Julia Delgado TascónChristof R Hauck
Jun 3, 2017·Scientific Reports·Kyle M SchachtschneiderLawrence B Schook
May 21, 2015·Journal of Leukocyte Biology·Julian WampflerMario P Tschan

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