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• W2108761729 endingPage "11186" @default.
• W2108761729 startingPage "11175" @default.
• W2108761729 abstract "Apoptosis-linked gene-2 (ALG-2) encodes a 22 kDa Ca2+-binding protein of the penta EF-hand family that is required for programmed cell death in response to various apoptotic agents. Here, we demonstrate that ALG-2 mRNA and protein are down-regulated in human uveal melanoma cells compared to their progenitor cells, normal melanocytes. The down regulation of ALG-2 may provide melanoma cells with a selective advantage. ALG-2 and its putative target molecule, Alix/AIP1, are localized primarily in the cytoplasm of melanocytes and melanoma cells independent of the intracellular Ca2+ concentration or the activation of apoptosis. Cross-linking and analytical centrifugation studies support a single-species dimer conformation of ALG-2, also independent of Ca2+ concentration. However, binding of Ca2+ to both EF-1 and EF-3 is necessary for ALG-2 interaction with Alix/AIP1 as demonstrated using surface plasmon resonance spectroscopy. Mutations in EF-5 result in reduced target interaction without alteration in Ca2+ affinity. The addition of N-terminal ALG-2 peptides, residues 1−22 or residues 7−17, does not alter the interaction of ALG-2 or an N-terminal deletion mutant of ALG-2 with Alix/AIP1, as might be expected from a model derived from the crystal structure of ALG-2. Fluorescence studies of ALG-2 demonstrate that an increase in surface hydrophobicity is primarily due to Ca2+ binding to EF-3, while Ca2+ binding to EF-1 has little effect on surface exposure of hydrophobic residues. Together, these data indicate that gross surface hydrophobicity changes are insufficient for target recognition." @default.
• W2108761729 created "2016-06-24" @default.
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• W2108761729 date "2004-08-12" @default.
• W2108761729 modified "2023-09-28" @default.
• W2108761729 title "Ca²⁺ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma" @default.
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• W2108761729 doi "https://doi.org/10.1021/bi048848d" @default.
• W2108761729 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1351334" @default.
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• W2108761729 hasPublicationYear "2004" @default.
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