Studies on the mechanism of the hepatitis B virus X protein (pX)-mediated apoptosis
Abstract
Apoptosis, or programmed cell death, is essential in development and homeostasis in multicellular organisms. Activation of the cellular stress pathways (JNK, p38) by environmental stresses is linked to apoptosis. The Hepatitis B virus X protein activates both p38 and JNK pathways, and in response to weak apoptotic signals, sensitizes hepatocytes to apoptosis. Employing tetracycline-regulated, pX-expressing hepatocyte cell lines, I investigated the mechanism of the combined p38 and JNK pathway activation in apoptosis. My results demonstrate that the combined activation of p38 and JNK pathways mediate pX-induced apoptosis, and suggest this mechanism of apoptosis occurs in vivo, in response to weak apoptotic signals. Furthermore, inhibition of the pX-dependent activation of the p38 MAP kinase and JNK pathways demonstrates the significance of the pX-activated mitogenic pathways in orchestrating the activation of p53 and its involvement in pX-mediated apoptosis. These results provide an in-depth mechanistic understanding of how stress pathways activate tumor suppressor p53 in response to a weak, viral oncogenic signal.
Degree
Ph.D.
Advisors
Andrisani, Purdue University.
Subject Area
Molecular biology
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