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

Publication ,  Journal Article
Jabbour, AM; Puryer, MA; Yu, JY; Lithgow, T; Riffkin, CD; Ashley, DM; Vaux, DL; Ekert, PG; Hawkins, CJ
Published in: J Cell Sci
June 15, 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.

Duke Scholars

Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

June 15, 2006

Volume

119

Issue

Pt 12

Start / End Page

2572 / 2582

Location

England

Related Subject Headings

  • bcl-2-Associated X Protein
  • Two-Hybrid System Techniques
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Protein Binding
  • Humans
  • Developmental Biology
  • Calcium-Binding Proteins
 

Citation

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Jabbour, A. M., Puryer, M. A., Yu, J. Y., Lithgow, T., Riffkin, C. D., Ashley, D. M., … Hawkins, C. J. (2006). Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1. J Cell Sci, 119(Pt 12), 2572–2582. https://doi.org/10.1242/jcs.02985
Jabbour, Anissa M., Michelle A. Puryer, Jai Y. Yu, Trevor Lithgow, Christopher D. Riffkin, David M. Ashley, David L. Vaux, Paul G. Ekert, and Christine J. Hawkins. “Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1.J Cell Sci 119, no. Pt 12 (June 15, 2006): 2572–82. https://doi.org/10.1242/jcs.02985.
Jabbour AM, Puryer MA, Yu JY, Lithgow T, Riffkin CD, Ashley DM, et al. Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1. J Cell Sci. 2006 Jun 15;119(Pt 12):2572–82.
Jabbour, Anissa M., et al. “Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1.J Cell Sci, vol. 119, no. Pt 12, June 2006, pp. 2572–82. Pubmed, doi:10.1242/jcs.02985.
Jabbour AM, Puryer MA, Yu JY, Lithgow T, Riffkin CD, Ashley DM, Vaux DL, Ekert PG, Hawkins CJ. Human Bcl-2 cannot directly inhibit the Caenorhabditis elegans Apaf-1 homologue CED-4, but can interact with EGL-1. J Cell Sci. 2006 Jun 15;119(Pt 12):2572–2582.
Journal cover image

Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

June 15, 2006

Volume

119

Issue

Pt 12

Start / End Page

2572 / 2582

Location

England

Related Subject Headings

  • bcl-2-Associated X Protein
  • Two-Hybrid System Techniques
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Protein Binding
  • Humans
  • Developmental Biology
  • Calcium-Binding Proteins