The proapoptotic function of SAP provides a clue to the clinical picture of X-linked lymphoproliferative disease.
Deletion or mutation of the SAP gene is associated with the X-linked lymphoproliferative disease (XLP) that is characterized by extreme sensitivity to Epstein-Barr virus (EBV). Primary infection of the affected individuals leads to serious, sometimes fatal infectious mononucleosis (IM) and proneness to lymphoma. Our present results revealed a proapoptotic function ... of SAP by which it contributes to the maintenance of T-cell homeostasis and to the elimination of potentially dangerous DNA-damaged cells. Therefore, the loss of this function could be responsible for the uncontrolled T-cell proliferation in fatal IM and for the generation of lymphomas. We show now the role of SAP in apoptosis in T and B lymphocyte-derived lines. Among the clones of T-ALL line, the ones with higher SAP levels succumbed more promptly to activation induced cell death (AICD). Importantly, introduction of SAP expression into lymphoblastoid cell lines (LCL) established from XLP patients led to elevated apoptotic response to DNA damage. Similar results were obtained in the osteosarcoma line, Saos-2. We have shown that the anti-apoptotic protein VCP (valosin-containing protein) binds to SAP, suggesting that it could be instrumental in the enhanced apoptotic response modulated by SAP.
Mesh Terms:
Adenosine Triphosphatases, Apoptosis, Biomarkers, Cell Cycle Proteins, Cell Line, Tumor, Cell Membrane, Cell Proliferation, Clone Cells, DNA Damage, G2 Phase, Gamma Rays, Genes, X-Linked, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Activation, Lymphoproliferative Disorders, Mitosis, Phytohemagglutinins, Protein Binding, Retroviridae, Signaling Lymphocytic Activation Molecule Associated Protein, T-Lymphocytes, Transduction, Genetic, Up-Regulation, Valosin Containing Protein, bcl-X Protein
Adenosine Triphosphatases, Apoptosis, Biomarkers, Cell Cycle Proteins, Cell Line, Tumor, Cell Membrane, Cell Proliferation, Clone Cells, DNA Damage, G2 Phase, Gamma Rays, Genes, X-Linked, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Activation, Lymphoproliferative Disorders, Mitosis, Phytohemagglutinins, Protein Binding, Retroviridae, Signaling Lymphocytic Activation Molecule Associated Protein, T-Lymphocytes, Transduction, Genetic, Up-Regulation, Valosin Containing Protein, bcl-X Protein
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 21, 2009
PubMed ID: 19570996
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