Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction.
ALG-2 is a 22-kDa calcium-binding protein necessary for cell death induced by different stimuli in 3DO T-cell hybridoma. 3DO cell clones depleted of ALG-2 protein exhibit normal caspases activation, suggesting that ALG-2 function is required downstream or is independent of caspase proteases activity for apoptosis to occur. Using the yeast two-hybrid screening system, we have isolated and characterized the mouse cDNA encoding for ALG-2 interacting protein 1 (AIP1), a novel protein that interacts with ALG-2. ALG-2 and AIP1 colocalize in the cytosol and the presence of calcium is an indispensable requisite for their association. Sequence alignment shows that AIP1 is highly similar to BRO1, a yeast protein related to components of the Pkc1p-MAP kinase cascade. Overexpression of a truncated form of AIP1 protects two different cell types from death induced by trophic factors withdrawal; thus, our data indicate that AIP1 cooperates with ALG-2 in executing the calcium-dependent requirements along the cell death pathway.
Vito
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T-cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. vito@mail.bii.ch
Pellegrini
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Guiet
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D'Adamio
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L
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011817:Rabbits; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C097753:PDCD6 protein, human; C117020:PDCD6IP protein, human; C490815:Pdcd6 protein, mouse; C492144:Pdcd6ip protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D002118:Calcium