Kang, ByoungAltieri, Dario C.2022-08-232022-08-232006-06-302008-08-04J Biol Chem. 2006 Aug 25;281(34):24721-7. Epub 2006 Jun 27. <a href="http://dx.doi.org/10.1074/jbc.M603175200">Link to article on publisher's site</a>0021-9258 (Print)10.1074/jbc.M60317520016807248https://hdl.handle.net/20.500.14038/42315Survivin 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.en-USAmino Acid MotifsAmino Acid SequenceCell DeathHela CellsHumansMicrotubule-Associated ProteinsMolecular Sequence DataNeoplasm ProteinsProtein BindingProtein TransportProteinsRNA InterferenceRecombinant ProteinsLife SciencesMedicine and Health SciencesJournal Articlehttps://escholarship.umassmed.edu/oapubs/676564485oapubs/676