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- Title
PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity.
- Authors
Tschan, M. P.; Reddy, V. A.; Ress, A.; Arvidsson, G.; Fey, M. F.; Torbett, B. E.
- 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 p21Cip1 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 p21Cip1.Oncogene (2008) 27, 3489–3493; doi:10.1038/sj.onc.1211004; published online 14 January 2008
- Subjects
MOUSE leukemia viruses; TRANSCRIPTION factors; HEMATOPOIETIC stem cells; BONE marrow cells; HEMATOPOIETIC system; FRIEND virus; BIOLOGICAL rhythms; LEUCOCYTOSIS
- Publication
Oncogene, 2008, Vol 27, Issue 24, p3489
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1211004