title: The proapoptotic function of SAP provides a clue to the clinical picture of X-linked lymphoproliferative disease.
abstract: 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.
authors: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Noémi
authors: N
authors: Nagy
authors: Liudmila
authors: L
authors: Matskova
authors: Loránd L
authors: LL
authors: Kis
authors: Ulf
authors: U
authors: Hellman
authors: George
authors: G
authors: Klein
authors: Eva
authors: E
authors: Klein
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells; D004249:DNA Damage; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D050172:Genes, X-Linked; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008232:Lymphoproliferative Disorders / Q000378:metabolism* / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D012190:Retroviridae; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D000074405:Valosin Containing Protein; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010835:Phytohemagglutinins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051020:bcl-X Protein; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein