Title

Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein

UMMS Affiliation

Department of Cancer Biology and the Cancer Center

Date

6-30-2006

Document Type

Article

Subjects

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

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Biol Chem. 2006 Aug 25;281(34):24721-7. Epub 2006 Jun 27. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

16807248