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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Jabbour, AM; Puryer, MA; Yu, JY; Lithgow, T; Riffkin, CD; Ashley, DM; Vaux, DL; Ekert, PG; Hawkins, CJ

Published Date

  • June 15, 2006

Published In

Volume / Issue

  • 119 / Pt 12

Start / End Page

  • 2572 - 2582

PubMed ID

  • 16735440

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.02985


  • eng

Conference Location

  • England