Regulation of Apoptosis.
Abstract
Apoptosis is a cellular suicide program which rids an organism of genetically damaged or superfluous cells. While apoptosis plays a critical role in development, tissue homeostasis and immune regulation, induction of this important cellular process is the mechanism of numerous chemotherapeutic drugs used in the treatment of breast and other cancers. In fact, the resistance of many tumors to chemotherapy often results from the inhibition of apoptosis usually induced in this treatment. Using the Xenopus egg extract in vitro system, we have previously identified crk, an adaptor protein which consists of one SH2 domain and two SH3 domains, as a necessary component in the apoptotic signaling pathway. Furthermore, we have established that when crk binding proteins are removed from the egg extract, apoptosis is inhibited. We have identified the Xenopus wee 1 protein, a known regulator of cell cycle kinases, as a specific crk SH2 binding protein using a recombinant crk SH2 affinity column and mass spectroscopic sequencing techniques. Xenopus weel binds specifically to the recombinant crk protein and isolated SH2 domain, and also co-immunoprecipitates with the crk protein from the egg extract. This represents the first known direct interaction between an adaptor-type signaling molecule and a cell cycle regulator. The function of Xenopus weel in the crk apoptotic signaling pathway is currently under investigation. We hope that this finding may provide one of the links between cell cycle progression and apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA364437
Entities
People
- Erica K. Evans
Organizations
- Duke University