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Initiation of Apaf-1 translation by internal ribosome entry

Oncogene volume 19, pages 899–905 (2000)Cite this article

Abstract

The apoptotic protease activating factor (Apaf-1) plays a central role in apoptosis: interaction of this protein with procaspase-9 leads to cleavage and activation of this initiator caspase. In common with other mRNAs whose protein products have a major regulatory function, the 5′ untranslated region (UTR) of Apaf-1 is long, G-C rich and has the potential to form secondary structure. We have shown that the 5′ UTR of Apaf-1 contains an internal ribosome entry segment, located in a 233 nucleotide region towards the 3′ end of the leader, and that the translation initiation of this mRNA occurs only by internal ribosome entry. The Apaf-1 IRES is active in almost all human cell types tested, including Human cervical carcinoma (HeLa), Human liver carcinoma (HepG2), Human breast carcinoma (MCF7), Human embryonic kidney (HK293), African Green Monkey kidney (COS7) and Human lung (MRC5). The Apaf-1 IRES initiates translation as efficiently as the HRV IRES, but is less active than the c-myc IRES. We propose that the Apaf-1 IRES ensures that a constant cellular level of Apaf-1 protein is maintained even under conditions where cap-dependent translation is compromised.

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Abbreviations

IRES:

internal ribosome entry segment

UTR:

untranslated region

Apaf-1:

Apoptotic protease activating factor-1

eIF:

eukaryotic initiation factor

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Acknowledgements

This work was supported by a grant from the Wellcome Trust number 055580 (SA Mitchell). MJ Coldwell holds an MRC studentship.

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Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, University Road, Leicester, LE1 7RH

    Mark J Coldwell, Sally A Mitchell, Mark Stoneley & Anne E Willis

  2. MRC Toxicology Unit, Hodgkin Building, University of Leicester, P.O. Box 138, Lancaster Road, Leicester, LE1 9HN

    Marion MacFarlane

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  1. Mark J Coldwell
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Coldwell, M., Mitchell, S., Stoneley, M. et al. Initiation of Apaf-1 translation by internal ribosome entry. Oncogene 19, 899–905 (2000). https://doi.org/10.1038/sj.onc.1203407

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