PMID- 12944970
OWN - NLM
STAT- MEDLINE
DCOM- 20030923
LR  - 20181130
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 424
IP  - 6952
DP  - 2003 Aug 28
TI  - Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in 
      Caenorhabditis elegans.
PG  - 1066-71
AB  - To ensure cell survival, it is essential that the ubiquitous pro-apoptotic 
      machinery is kept quiescent. As death is irreversible, cells must continually 
      integrate developmental information with regulatory inputs to control the switch 
      between repressing and activating apoptosis. Inappropriate activation or 
      suppression of apoptosis can lead to degenerative pathologies or tumorigenesis, 
      respectively. Here we report that Caenorhabditis elegans inhibitor of cell 
      death-1 (ICD-1) is necessary and sufficient to prevent apoptosis. Loss of ICD-1 
      leads to inappropriate apoptosis in developing and differentiated cells in 
      various tissues. Although this apoptosis requires CED-4, it occurs independently 
      of CED-3--the caspase essential for developmental apoptosis--showing that these 
      core pro-apoptotic proteins have separable roles. Overexpressing ICD-1 inhibits 
      the apoptosis of cells that are normally programmed to die. ICD-1 is the 
      beta-subunit of the nascent polypeptide-associated complex (betaNAC) and contains 
      a putative caspase-cleavage site and caspase recruitment domain. It localizes 
      primarily to mitochondria, underscoring the role of mitochondria in coordinating 
      apoptosis. Human betaNAC is a caspase substrate that is rapidly eliminated in 
      dying cells, suggesting that ICD-1 apoptosis-suppressing activity may be 
      inactivated by caspases.
FAU - Bloss, Tim A
AU  - Bloss TA
AD  - Department of Molecular, Cellular and Developmental Biology, University of 
      California, Santa Barbara, California 93106, USA.
FAU - Witze, Eric S
AU  - Witze ES
FAU - Rothman, Joel H
AU  - Rothman JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Ced-4 protein, C elegans)
RN  - 0 (Ced-9 protein, C elegans)
RN  - 0 (ICD-1 protein, C elegans)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Trans-Activators)
RN  - 0 (nascent-polypeptide-associated complex)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (ced-3 protein, C elegans)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Caenorhabditis elegans/*cytology/embryology/*metabolism
MH  - Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism
MH  - Calcium-Binding Proteins/genetics/metabolism
MH  - Caspases/genetics/metabolism
MH  - Heat-Shock Response
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/cytology
MH  - Mitochondria/chemistry/*metabolism
MH  - Molecular Chaperones
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Neurons/cytology/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - RNA Interference
MH  - Trans-Activators/chemistry/genetics/*metabolism
EDAT- 2003/08/29 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/08/29 05:00
PHST- 2003/01/06 00:00 [received]
PHST- 2003/07/22 00:00 [accepted]
PHST- 2003/08/29 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/08/29 05:00 [entrez]
AID - nature01920 [pii]
AID - 10.1038/nature01920 [doi]
PST - ppublish
SO  - Nature. 2003 Aug 28;424(6952):1066-71. doi: 10.1038/nature01920.