I received my Ph.D. in Dr. Michael Smerdon's lab at Washington State University, Pullman, WA. I have extensive training in DMA damage and repair in the context of chromatin environment. During the past five years, I have been working on the functional regulation of mammalian Polo-like kinase (Plk1) under the supervision of Dr. Raymond Erikson, Harvard University. Genetic and biochemical experiments with several different organisms have demonstrated that polo-like kinases are involved in many aspects of cell cycle related events. A close correlation between mammalian Plk1 expression and carcinogenesis was recently documented. Over expression of Plk1 was observed in various human tumors, and Plk1 was proposed to be a novel diagnostic marker for several types of cancers. Thus, inhibition of Plk1 function may be an important application for cancer therapy, and it is of clinical significance to understand the molecular mechanism of Plk1 and its interacting proteins. My long-term goal is to understand the functional regulation of Plk1. A yeast two-hybrid system was used to identify the CCT chaperonin complex as a Plk1 interacting partner. Whether CCT is required for the biogenesis of functional Plk1 is going to be tested with the highest priority. We previously reported the phenotype resulting from Plk1 depletion using RNAi and found that Plk1 depletion induces G2/M arrest and apoptosis in cancer cells. We propose to continue our analysis of Plk1 depletion induced phenotype in primary cells using the lentivirus-based RNAi as well as to determine the molecular events that lead to DMA damage in the absence of Plkl In the last part of the proposed study, we will analyze the functional significance of Plk1 -associated phosphorylation of Mklp-1 and the chromokinesin, Kid. The involvement of the nuclear localization signal on Mklp-1 function during cell division and the effect of Plk1 phosphorylation on microtubule bundling activity of Mklp-1 will be examined. Kid also appears to be a novel Plk1 substrate. Whether the function of Kid during mitosis is affected by Plk1 will be analyzed.
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