A comparison of the expression and properties of Apaf-1 and Apaf-1L.
Apaf-1 is a mammalian homolog of CED-4 that regulates cell death by participating in a ternary complex with cytochrome c, and procaspase-9. In the case of CED-4, two splice variants exist. The smaller (CED-4S) is proapoptotic while the larger (CED-4L) contains a short in-frame insert and is anti-apoptotic. We cloned a murine variant of apaf-1, termed apaf-1L, which contains an eleven amino acid insert similar to a recently described human apaf-1L clone. apaf-1 and apaf-1L have similar distributions in adult and fetal tissues, although apaf-1L transcripts are more abundant. Apaf-1L, undergoes homomerization and heteromerization with Apaf-1 in yeast. Apaf-1L also binds to caspase-9 and a dominant-negative isoform of caspase-9. Unlike CED-4, neither Apaf-1 variant was lethal in yeast. However, both Apaf-1 and Apaf-1L elicit cell death when cotransfected with caspase-9 into 293 EBNA cells. Although Apaf-1L was more potent than Apaf-1, their biological properties were qualitatively similar.
Walke
D W
DW
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 N. Lauderdale St., 38105-2794, Memphis, TN, USA.
Morgan
J I
JI
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004792:Enzyme Precursors / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics; D051379:Mice; D009928:Organ Specificity; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020798:Two-Hybrid System Techniques
C506592:APAF1 protein, human; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D004792:Enzyme Precursors; D015801:Helminth Proteins; D020033:Protein Isoforms; D011506:Proteins; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases