Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein.
ALG-2 is a EF hand calcium binding protein with sequence homologies to calmodulin. Vito et al have shown that ALG-2 expression is required for apoptosis following a number of death stimuli,1 although nothing is known about the effectors which underlie ALG-2 function. Here we have used ALG-2 as bait in a yeast two hybrid screen of a mouse brain cDNA library. We found that ALG-2 binds to itself and to a novel protein that we call ALG-2 interacting protein X, Alix. Using co-immunoprecipitation experiments, we confirmed ALG-2/ALG-2 binding and demonstrated that this interaction is calcium independent. ALG-2/Alix interaction was also validated by co-immunoprecipitation, but in this case, the binding was found to be strictly calcium dependent. Alix seems highly conserved throughout evolution since it shows significant homologies to a putative C. elegans protein (YNK-1) and to proteins of A. nidulans (PalA) and S. cerevisiae (BRO1). Alix is a potential regulator or downstream effector of ALG-2 action.
Missotten
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Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland.
Nichols
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Rieger
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Sadoul
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R
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C109773:ALX-1 protein, C elegans; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D005656:Fungal Proteins; D018398:Homeodomain Proteins; C104643:PALA protein, Emericella nidulans; C490815:Pdcd6 protein, mouse; C492144:Pdcd6ip protein, mouse; D012333:RNA, Messenger; D002118:Calcium