Regulation of Fas ligand expression and cell death by apoptosis-linked gene 4.
Programmed cell death is a process required for the normal development of an organism. One of the best understood apoptotic pathways occurs in T lymphocytes and is mediated by Fas/Fas ligand (FasL) interaction. During studies of apoptosis induced by T cell-receptor engagement, we identified ALG-4F, a truncated transcript that prevents T cell-receptor-induced FasL upregulation and cell death. Overexpression of full-length ALG-4 induced transcription of FasL and, consequently, apoptosis. These results indicate that ALG-4 is necessary and sufficient for FasL expression. Fas/FasL interaction initiates cell death in many other systems, and its dysregulation is a mechanism by which several pathologic conditions arise. Understanding the molecular mechanisms of FasL regulation could be very useful in elucidating how these diseases develop and in identifying potential therapeutic targets.
Lacana
E
E
T-cell Apoptosis Unit, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
D'Adamio
L
L
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D020169:Caspases / Q000032:analysis; D053222:Fas Ligand Protein; D017930:Genes, Reporter; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; C118864:Pdcd11 protein, mouse; D011948:Receptors, Antigen, T-Cell; D020169:Caspases