| Cell death is an important biological process that selectively eliminates cells in developing embryo as well as in adult tissues. The mechanisms underlying this selective elimination are still unclear. The aim of this work has been to study the role of cyclin-dependent kinase 5 (Cdk5) in cell death. Several established cell death models have been used in this work, which include normally developing limb and developing lens, abnormally developing cyclophosphamide (CP), an alkylating agent, treated embryo, and toxic compounds induced cell strain (COS-7) cell death.; To address the role of Cdk5 in cell death, we, first, investigated the regulation of Cdk5 from the transcription, translation, and post-translation levels and the results showed that Cdk5 was activated at the post-translation level. Second, to identify how Cdk5 was regulated by other proteins, a yeast two-hybrid system and 35S-Met incorporation immunoprecipitation technique were used. From both approaches, p35 and its truncated form, p25, were identified to be associated with Cdk5. Furthermore, we investigated the pattern of p35/p25 expression, and the results showed that both p35 and p25 had similar expression pattern as Cdk5 during cell death. Further study indicates that during cell death, p35 could be truncated to p25, and p25 might be the factor, which activates Cdk5 during cell death. These results suggested that Cdk5 and its regulatory proteins may be key players in the execution of cell death. |
