Sci. STKE, 21 May 2002
Apoptosis Uncovering an Interaction Between Cyclin D3 and Caspase 2
Cells' survival is dependent on their maintaining a balance. Stimuli that typically produce proliferation can sometimes lead to apoptosis if this balance is not achieved. Mendelsohn et al. identified an interaction between cyclin D3 and caspase 2 using a traditional yeast two-hybrid assay. This interaction was confirmed by coprecipitation from cells transfected with epitoped-tagged caspase 2 and epitope-tagged cyclin D3. When cyclin D3 and caspase 2 were coexpressed in transfected cells, more cells died than when they were only expressing caspase 2, suggesting that cyclin D3 may stimulate caspase 2 activation. In cells overexpressing cyclin D3, there was an increase in the ratio of cleaved to uncleaved caspase 2. Finally, the authors used an assay to identify mutants of caspase 2 that do not interact with the cyclin. Expression of these mutants showed that these mutant caspase 2 proteins did not promote cell death and were not cleaved when cyclin D3 was present. The mutant caspase 2 proteins were capable of cleavage, because coexpression of wild-type caspase 2 resulted in cleavage and stimulated cell death. Thus, the authors uncovered a link between cell proliferation and cell death. They also demonstrated the use of a screen to identify noninteracting mutations in protein partners.
A. R. Mendelsohn, J. D. Hamer, Z. B. Wang, R. Brent, Cyclin D3 activates caspase 2, connecting cell proliferation with cell death. Proc. Natl. Acad. Sci. U.S.A. 99, 6871-6876 (2002). [Abstract] [Full Text]
Citation: Uncovering an Interaction Between Cyclin D3 and Caspase 2. Sci. STKE 2002, tw185 (2002).
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