Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein
Department of Cancer Biology and the Cancer Center
Amino Acid Motifs; Amino Acid Sequence; Cell Death; Hela Cells; Humans; Microtubule-Associated Proteins; Molecular Sequence Data; Neoplasm Proteins; Protein Binding; Protein Transport; Proteins; RNA Interference; Recombinant Proteins
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Biol Chem. 2006 Aug 25;281(34):24721-7. Epub 2006 Jun 27. Link to article on publisher's site
The Journal of biological chemistry
Kang, Byoung and Altieri, Dario C., "Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein" (2006). Open Access Articles. 676.