title: FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.
abstract: We identified and cloned a novel human protein that contains FADD/Mort1 death effector domain homology regions, designated FLAME-1. FLAME-1, although most similar in structure to Mch4 and Mch5, does not possess caspase activity but can interact specifically with FADD, Mch4, and Mch5. Interestingly, FLAME-1 is recruited to the Fas receptor complex and can abrogate Fas/TNFR-induced apoptosis upon expression in FasL/tumor necrosis factor-sensitive MCF-7 cells, possibly by acting as a dominant-negative inhibitor. These findings identify a novel endogenous control point that regulates Fas/TNFR1-mediated apoptosis.
authors.affiliation: Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Srinivasula
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: S
authors.initials: S
authors.lastname: Ottilie
authors.forename: F
authors.initials: F
authors.lastname: Bullrich
authors.forename: S
authors.initials: S
authors.lastname: Banks
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Fernandes-Alnemri
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: G
authors.initials: G
authors.lastname: Litwack
authors.forename: K J
authors.initials: KJ
authors.lastname: Tomaselli
authors.forename: R C
authors.initials: RC
authors.lastname: Armstrong
authors.forename: E S
authors.initials: ES
authors.lastname: Alnemri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D047990:TNF Receptor-Associated Factor 1; D014018:Tissue Distribution; D014466:Ultraviolet Rays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D047990:TNF Receptor-Associated Factor 1; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; C506438:CASP10 protein, human