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Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67

Majumdar, Avijit
http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

Abstract Details

2008, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
The eukaryotic initiation factor 2 associated glycoprotein p67 plays an important role in the regulation of global protein synthesis by modulating the phosphorylation of the smallest α subunit of eIF2. Recently it has been shown that treatment of the mouse myoblast cells with anti-angiogenic drug fumagillin stabilizes p67 which in turn causes a decrease in the phosphorylation of ERK 1 & 2 upon direct binding. Analysis of the role of p67 in the regulation of ERK 1& 2 MAP kinase pathway shows that it can inhibit the activation of ERK1 & 2 stimulated by 1. Epidermal growth factor (EGF) 2. Constitutively active MEK (MEKA) 3. Oncogenic K-RasV12. It has also been shown that p67 can act as a tumor suppressor protein as it can inhibit the cell growth of the oncogenic K-RasV12 transformed NIH3T3 cells in normal medium and medium containing low serum. P67 also decreases the number of foci formation by the oncogenic K-RasV12 transformed cells and causes a regression of tumor formation when injected in athymic mice. P67, when exogenously expressed, decreases the induced expression of cyclin D1 in the oncogenic K-RasV12 transformed NIH3T3 cells. These data support p67's potential to function as a tumor suppressor protein. The down regulation of the endogenous p67 by siRNA causes an induction of the activation of ERK 1 & 2. Analysis of the molecular details of the interaction of p67 with ERK 1 & 2 shows that the N-terminal 1-336 amino acid segment of p67 binds to ERK 1 & 2 in vivo and in vitro. On the other hand the C terminal 150-358 amino acid segment of ERK2 is needed for binding with p67. We have also shown the existence of a tri-complex involving p67, ERK2 & MEK1 and p67 can inhibit the oncogenic KRasV12 induced activation of MEK.
Bansidhar Datta, PhD (Committee Chair)
Gail Fraizer, PhD (Committee Member)
Srinivasan Vijayaraghavan, PhD (Committee Member)
Sean Veney, PhD (Committee Member)
171 p.
Biomedical Research; Cellular Biology; Molecular Biology
P67; ERK1; ERK2; Oncogenic KRasV12; Tumor suppressor

Recommended Citations

Citations

  • Majumdar, A. (2008). Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67 [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

    APA Style (7th edition)

  • Majumdar, Avijit. Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67. 2008. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031.

    MLA Style (8th edition)

  • Majumdar, Avijit. "Regulation of the Activation and Activity of the Extra-cellular Signal Regulated Kinases 1 & 2 MAP Kinase Pathway by Eukaryotic Initiation Factor 2 Associated Glycoprotein P67." Doctoral dissertation, Kent State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=kent1209000031

    Chicago Manual of Style (17th edition)

kent1209000031
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© 2008, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.