QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 30 May 2006
doi: 10.1242/jcs.02985

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.02985v1 119/12/2572    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jabbour, A. M. Articles by Hawkins, C. J. Search for Related Content PubMed PubMed Citation Articles by Jabbour, A. M. Articles by Hawkins, C. J.

Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1

¹ Children's Cancer Centre, Royal Children's Hospital, Parkville 3052, Australia
² Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3052, Australia
³ Department of Paediatrics, University of Melbourne, Parkville 3010, Australia
⁴ Walter and Eliza Hall Institute, Royal Melbourne Hospital, Parkville 3050, Australia
⁵ Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville 3010, Australia
⁶ Department of Biochemistry, La Trobe University, Bundoora 3086, Australia
⁷ Department of Neonatology, Royal Children's Hospital, Parkville 3052, Australia

^* Author for correspondence (e-mail: c.hawkins{at}latrobe.edu.au)

Accepted 21 March 2006

Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action is still incompletely understood. In the nematode Caenorhabditis elegans, 131 of 1090 somatic cells undergo programmed cell death during development. Transgenic expression of human Bcl-2 reduced cell death during nematode development, and partially complemented mutation of ced-9, indicating that Bcl-2 can functionally interact with the nematode cell death machinery. Identification of the nematode target(s) of Bcl-2 inhibition would help clarify the mechanism by which Bcl-2 suppresses apoptosis in mammalian cells. Exploiting yeast-based systems and biochemical assays, we analysed the ability of Bcl-2 to interact with and regulate the activity of nematode apoptosis proteins. Unlike CED-9, Bcl-2 could not directly associate with the caspase-activating adaptor protein CED-4, nor could it inhibit CED-4-dependent yeast death. By contrast, Bcl-2 could bind the C. elegans pro-apoptotic BH3-only Bcl-2 family member EGL-1. These data prompt us to hypothesise that Bcl-2 might suppress nematode cell death by preventing EGL-1 from antagonising CED-9, rather than by inhibiting CED-4.

Key words: Apoptosis, Caspase, Ced-9, Programmed Cell Death, Saccharomyces Cerevisiae