Journal Article

Wild-type p53 activates SAP expression in lymphoid cells

Kis, L L, Takahara, M, Nishikawa, J, Klein, E, Klein, G, Nagy, N, Bourdon, J C

2004

Overview

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- α . 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 suggest that SAP contributes to the execution of some p53 functions.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Adaptor proteins / Apoptosis / Base Sequence / Biological and medical sciences / Burkitt Lymphoma / Burkitt's lymphoma / CD150 antigen / Cell Biology / Cell cycle / Cell growth / Cell Line, Tumor / Cell physiology / Cell proliferation / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / DNA Damage / Epstein-Barr virus / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Regulation - drug effects / Hematologic and hematopoietic diseases / Human Genetics / Humans / Immunodeficiency / Immunoproliferative diseases / Infections / Internal Medicine / Intracellular Signaling Peptides and Proteins - genetics / Intracellular Signaling Peptides and Proteins - metabolism / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Lymphoblastoid cell lines / Lymphocytes / Lymphocytes - drug effects / Lymphocytes - metabolism / Lymphocytes - pathology / Lymphocytes - radiation effects / Lymphocytes B / Lymphoid cells / Lymphoma / Medical sciences / Medicine / Medicine & Public Health / Molecular and cellular biology / Molecular Sequence Data / mRNA / Mutation - genetics / Oncology / original-paper / p53 Protein / Phytohemagglutinins - pharmacology / Primary immunodeficiencies / Promoter Regions, Genetic - genetics / Proteins / Response Elements - genetics / RNA, Messenger - genetics / RNA, Messenger - metabolism / Signal transduction / Signaling Lymphocytic Activation Molecule Associated Protein / T-Lymphocytes - drug effects / T-Lymphocytes - metabolism / T-Lymphocytes - radiation effects / Temperature / Tumor Suppressor Protein p53 - chemistry / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism / Up-Regulation - drug effects