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

Tschan, M P; Reddy, V A; Ress, A; Arvidsson, G; Fey, M F; Torbett, B E (2008). PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity. Oncogene, 27(24), pp. 3489-93. Basingstoke, UK: Nature Publishing Group 10.1038/sj.onc.1211004

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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).

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
UniBE Contributor:	Tschan, Mario Paul, Ress, Angelika, Fey, Martin
ISSN:	0950-9232
ISBN:	18193090
Publisher:	Nature Publishing Group
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:02
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1038/sj.onc.1211004
PubMed ID:	18193090
Web of Science ID:	000256309900014
URI:	https://boris.unibe.ch/id/eprint/27113 (FactScience: 102655)