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.
MeSH Terms
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Apoptosis/drug effects,radiation effects
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins/chemistry,genetics,metabolism
Caspase 10
Caspase 8
Caspase 9
Caspases
Cloning, Molecular
Cysteine Endopeptidases/chemistry,metabolism
Fas Ligand Protein
Fas-Associated Death Domain Protein
Humans
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins/metabolism
Molecular Sequence Data
Proteins/metabolism
Sequence Homology, Amino Acid
TNF Receptor-Associated Factor 1
Tissue Distribution
Ultraviolet Rays
Chemicals
Adaptor Proteins, Signal Transducing
CASP8 and FADD-Like Apoptosis Regulating Protein
CFLAR protein, human
Carrier Proteins
FADD protein, human
FASLG protein, human
Fas Ligand Protein
Fas-Associated Death Domain Protein
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
Proteins
TNF Receptor-Associated Factor 1
CASP8 protein, human
CASP9 protein, human
Caspase 10
Caspase 8
Caspase 9
Caspases
Cysteine Endopeptidases
CASP10 protein, human
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Srinivasula S M
Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Ahmad M
Ottilie S
Bullrich F
Banks S
Wang Y
Fernandes-Alnemri T
Croce C M
Litwack G
Tomaselli K J
Armstrong R C
Alnemri E S