Role of cdc25 Phosphatases in Cellular Immortalization
Annual rept. 23 Mar 1999-22 Mar 2000
BAYLOR COLL OF MEDICINE HOUSTON TX
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The goal of this proposal is to study the potential role of tyrosine phosphorylation-dependent checkpoint and especially the cdc25 phosphatase family of cyclin dependent kinase CDK activators in cellular immortalization. We have shown that cdc25 phosphatases did in fact extend the normal mammary epithelial cells HMEC life span, but do not immortalize them. The effect was most prominent with cdc25A and cdc25B phosphatases. Cdc25C phosphatase had less effect on HMEC life span. Experiments with catalytically inactive cdc25A mutant show that phosphatase activity of cdc25A is essential for the life span extension. Our experiments show that telomerase is not activated by cdc25A expression in normal human cells, suggesting that cdc25 most likely affect Ml, but not M2 checkpoints. Retroviral cDNA libraries sense and anti-sense were introduced into HMEC together with cdc25 to assay for the potential enhancement of cdc25 ability to expand the cellular life span. Work is underway to identify genes affected by the appropriate antisense constructs.
- Anatomy and Physiology
- Medicine and Medical Research