title: Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein.
abstract: Survivin is a multifunctional member of the IAP (inhibitor of apoptosis) family, but its molecular interactions in protection from cell death and regulation of cell division have not been completely elucidated. In a proteomics screening to identify novel survivin-binding partners, we found that the aryl hydrocarbon receptor-interacting protein (AIP) directly associates with survivin in vitro and in co-immunoprecipitation experiments in vivo. This interaction is mediated by the carboxyl-terminal end of AIP, which contains three tetratricopeptide motifs, and involves the carboxyl terminus coiled coil in survivin with critical roles of Asp(142) in AIP recognition. A survivin mutant lacking only Asp(142) fails to bind AIP and exhibits accelerated degradation in vivo in a reaction reversed by a proteasome inhibitor. Acute knock-down of AIP by short interference RNA or competition of the survivin-AIP complex by peptidyl mimicry destabilizes survivin levels in cells, with enhanced apoptosis but no changes in cell cycle progression. Therefore, AIP regulates survivin stability, thus elevating a cellular anti-apoptotic threshold. The survivin-AIP complex may influence the cellular xenobiotic response to environmental toxin(s) and contribute to subcellular chaperone trafficking during cell death regulation.
authors.affiliation: Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Byoung Heon
authors.initials: BH
authors.lastname: Kang
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016923:Cell Death / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011994:Recombinant Proteins; D000077022:Survivin; C103265:aryl hydrocarbon receptor-interacting protein