Dissertation
Pim kinases phosphorylate p21 CiP1/WAF1 and c-Myc
Washington State University
Doctor of Philosophy (PhD), Washington State University
08/2007
DOI:
https://doi.org/10.7273/000005689
Abstract
Pim protein kinases are a distinct class of Serine/Threonine protein kinases which
play very important roles in growth factor signaling. They have been shown to be highly
expressed in a variety of primary tumors, especially associated with the development of
leukemia and prostate cancer. Transgenic mice with knockdown of Pim kinases have
been shown to have a dramatic reduced body size while overexpression of Pim kinases
has been shown to promote cancer development. In order to better address the possible mechanism in tumorigenesis caused by Pim kinases, p21Cip1/WAF was studied as one of the prominent substrates of Pim kinases. As a continuation of previous results, the thesis mainly tries to explore the functional consequences after Pim kinases phosphorylate p21Cip1/WAF1. In a non-small cell lung carcinoma cell line, H1299, overexpression of Pim-1 has been shown to influence the stability, cellular localization of p21 and subsequently promotes cell proliferation. While in a human colon cancer cell line, HCT116, enforced expression of Pim-2 kinase causes the stabilization of p21Cip1/WAF1 in the nucleus which promotes cell survival after cells have been sensitized to apoptosis by simultaneous overexpression of c-myc during DNA damage. In addition, the thesis provides preliminary evidence that Pim kinases phosphorylate c-Myc and stabilize it. These results may partially explain the synergistic activity between c-Myc and Pim kinases in tumorigenesis.
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Details
- Title
- Pim kinases phosphorylate p21 CiP1/WAF1 and c-Myc
- Creators
- Yandong Zhang
- Contributors
- Nancy S Magnuson (Chair) - Washington State University, School of Molecular BiosciencesChulHee Kang (Committee Member) - Washington State University, Department of ChemistryJames E. Bruce (Committee Member)Raymond Reeves (Committee Member) - Washington State University, School of Molecular Biosciences
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 139
- Identifiers
- 99901054758401842
- Language
- English
- Resource Type
- Dissertation