Editors' ChoiceTranslation Control

Translating Apoptosis

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Science's STKE  23 Apr 2002:
Vol. 2002, Issue 129, pp. tw155
DOI: 10.1126/stke.2002.129.tw155

During apoptosis, overall rates of translation are generally decreased, but translation of certain proteins actually increases. Translation of these proteins, which include important regulatory molecules like the oncogene product c-Myc, Apaf-1 (apoptotic protease-activating factor 1), and death-associated protein 5 [DAP5, a member of the translation initiation factor 4G (eIF4G) family], is initiated through IRES (internal ribosome entry site) elements. DAP5 and other eIF4G proteins are cleaved by caspases during apoptosis. Henis-Korenbilt et al. show that such cleavage of DAP5 removes an inhibitory effect of the COOH-terminus of the protein and enhances cap-independent translation of DAP5 itself, c-Myc, XIAP (X-linked inhibitor of apoptosis), and Apaf-1. Caspase activation thus appears to control translation directly through DAP5. Such regulation sets up complex feedback loops, producing more DAP5 protein itself and enhancing the synthesis of both proapoptotic and antiapoptotic proteins.

S. Henis-Korenblit, G. Shani, T. Sines, L. Marash, G. Shohat, A. Kimchi, The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins. Proc. Natl. Acad. Sci. U.S.A. 99, 5400-5405 (2002). [Full Text] [Abstract]

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