PMID- 10542291
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - F1Aalpha, a death receptor-binding protein homologous to the Caenorhabditis
      elegans sex-determining protein, FEM-1, is a caspase substrate that mediates
      apoptosis.
PG  - 32461-8
AB  - Apoptosis is an evolutionarily conserved process that is critical for tissue
      homeostasis and development including sex determination in essentially all
      multicellular organisms. Here, we report the cloning of an ankyrin
      repeat-containing protein, termed F1Aalpha, in a yeast two-hybrid screen using
      the cytoplasmic domain of Fas (CD95/APO-1) as bait. Amino acid sequence analysis 
      indicates that F1Aalpha has extensive homology to the sex-determining protein
      FEM-1 of the Caenorhabditis elegans, which is required for the development of all
      aspects of the male phenotype. F1Aalpha associates with the cytoplasmic domains
      of Fas and tumor necrosis factor receptor 1, two prototype members of the "death 
      receptor" family. The F1Aalpha protein also oligomerizes. Overexpression of
      F1Aalpha induces apoptosis in mammalian cells, and co-expression of Bcl-XL or the
      dominant negative mutants of either FADD or caspase-9 blocks this effect.
      Deletion analysis revealed the center region of F1Aalpha, including a cluster of 
      five ankyrin repeats to be necessary and sufficient for maximum apoptotic
      activity, and the N-terminal region appears to regulate negatively this activity.
      Furthermore, F1Aalpha is cleaved by a caspase-3-like protease at Asp(342), and
      the cleavage-resistant mutant is unable to induce apoptosis upon overexpression. 
      F1Aalpha is therefore a member of a growing family of death receptor-associated
      proteins that mediates apoptosis.
FAU - Chan, S L
AU  - Chan SL
AD  - Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609,
      Republic of Singapore.
FAU - Tan, K O
AU  - Tan KO
FAU - Zhang, L
AU  - Zhang L
FAU - Yee, K S
AU  - Yee KS
FAU - Ronca, F
AU  - Ronca F
FAU - Chan, M Y
AU  - Chan MY
FAU - Yu, V C
AU  - Yu VC
LA  - eng
SI  - GENBANK/AF178632
SI  - GENBANK/AF178633
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (FEM-1 protein, C elegans)
RN  - 0 (FEM1B protein, human)
RN  - 0 (Peptide Library)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (bcl-X Protein)
RN  - 0 (fas Receptor)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (Fad7 protein, Arabidopsis)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - *Apoptosis
MH  - *Arabidopsis Proteins
MH  - Caenorhabditis elegans
MH  - *Caenorhabditis elegans Proteins
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Caspases/*metabolism
MH  - Cell Cycle Proteins/*chemistry
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Fatty Acid Desaturases/metabolism/pharmacology
MH  - Female
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Peptide Library
MH  - Proto-Oncogene Proteins c-bcl-2/pharmacology
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Sequence Homology, Amino Acid
MH  - Tumor Cells, Cultured
MH  - Yeasts
MH  - bcl-X Protein
MH  - fas Receptor/metabolism
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32461 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32461-8. doi: 10.1074/jbc.274.45.32461.