Wild-type p53 activates SAP expression in lymphoid cells

Oncogene
N NagyE Klein

Abstract

SAP is an adaptor molecule with one SH2 domain and it is expressed in activated T and NK cells, where it is required for the appropriate signaling from the SLAM family of surface receptors. Deleted or mutated SAP genes that encode functionally defective protein are associated with the X-linked lymphoproliferative disease (XLP). This primary immunodeficiency is characterized by extreme sensitivity to Epstein-Barr virus (EBV) infection, dysgammaglobulinemia and a high rate of lymphoma development. The vigorous T- and B-cell proliferation that follows EBV infection and the high incidence of lymphomas (30%) in XLP patients might reflect functional defects in cell cycle and/ or apoptosis control. Our experiments show that SAP is a target of p53. In Burkitt lymphoma (BL) lines transfected with a temperatur-sensitive (ts) p53, SAP mRNA and protein expression was dependent on wild-type (wt) p53. Activation of endogenous wt p53 in BLs and lymphoblastoid cell lines led to the induction of SAP and this was inhibited by the specific p53 inhibitor pifithrin-alpha. Cell lines that carried mutant p53 did not express SAP under similar conditions. Moreover, we have shown binding of wt p53 to the promoter region of SAP by ChIP assay. Our results...Continue Reading

References

Apr 1, 1987·Annals of Internal Medicine·H Grierson, D T Purtilo
Apr 15, 1987·Cancer·D S HarringtonD T Purtilo
Dec 15, 1982·International Journal of Cancer. Journal International Du Cancer·S HaradaD T Purtilo
Oct 1, 1995·Pediatric Research·T A SeemayerJ Sumegi
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·K E NicholsD A Haber
Jun 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·B S SyllaE Kieff
Apr 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·L M ShlapatskaS P Sidorenko
Jun 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·M J CzarP L Schwartzberg
Jan 25, 2003·Nature Cell Biology·Betty ChanMichael J Eck
Mar 28, 2003·The EMBO Journal·Vassilis G GorgoulisAthanasios G Papavassiliou

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Citations

Jul 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Noémi NagyEva Klein
Jan 12, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Elena A Ostrakhovitch, Shawn S-C Li
Aug 7, 2008·Blood·Andrew J SteeleR Gitendra Wickremasinghe
Jan 20, 2009·Cellular Signalling·Elena A OstrakhovitchShawn S-C Li
Dec 9, 2014·Cell Cycle·Martin FischerKurt Engeland
Nov 21, 2012·Cell Cycle·Harsha S MadapuraNoémi Nagy
May 17, 2017·Leukemia & Lymphoma·Sergey A DyshlovoyGunhild von Amsberg

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