Publication Date:
1998-08-28
Description:
Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, X -- Chang, H Y -- Baltimore, D -- CA51462/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 28;281(5381):1355-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9721101" target="_blank"〉PubMed〈/a〉
Keywords:
*Apoptosis
;
Apoptosis Regulatory Proteins
;
Biopolymers
;
*Caenorhabditis elegans Proteins
;
Calcium-Binding Proteins/*chemistry/genetics/*metabolism
;
*Caspases
;
Cell Line
;
Chemistry, Physical
;
Cysteine Endopeptidases/*metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Enzyme Activation
;
Enzyme Precursors/metabolism
;
HeLa Cells
;
Helminth Proteins/*chemistry/genetics/*metabolism
;
Humans
;
Mutation
;
Oligopeptides/pharmacology
;
Physicochemical Phenomena
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-bcl-2/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Tacrolimus/pharmacology
;
Transfection
;
bcl-X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
