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Inhibitor of apoptosis (IAP) proteins, which bind to caspases via their baculoviral IAP repeat domains, also bear RING domains that enable them to promote ubiquitylation of themselves and other interacting proteins. Here we show that the RING domain of cIAP1 allows it to bind directly to the RING of X-linked IAP, causing its ubiquitylation and degradation by the proteasome, thus revealing a mechanism by which IAPs can regulate their abundance. Expression of a construct containing the RING of cellular IAP1 was able to deplete melanoma cells of endogenous X-linked IAP, promoted apoptosis, and also markedly reduced their clonogenicity when treated with cisplatin. Cross control of protein levels by RING domains may therefore enable their levels to be manipulated therapeutically.

Original publication

DOI

10.1073/pnas.0502828102

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

08/11/2005

Volume

102

Pages

16182 - 16187

Keywords

Amino Acid Sequence, Apoptosis, Caspases, Cell Line, Cell Survival, Cisplatin, Homeostasis, Inhibitor of Apoptosis Proteins, Melanoma, Molecular Sequence Data, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Ubiquitin-Protein Ligases, X-Linked Inhibitor of Apoptosis Protein