Chapters authored
The Key Role of E2F in Tumor Suppression through Specific Regulation of Tumor Suppressor Genes in Response to Oncogenic Changes
E2F, the principal target of the tumor suppressor pRB, plays crucial roles in tumor suppression. Upon dysfunction of pRB, E2F activates tumor suppressor genes such as ARF, an upstream activator of the tumor suppressor p53, resulting in the induction of apoptosis and tumor suppression. The E2F activity that activates the tumor suppressor genes is detected only in cancer cells and not in normal growing cells. The E2F activity can drive selective suicide gene expression and induce apoptosis specifically in cancer cells. Thus, the E2F activity provides a beneficial tool to specifically target cancer cells in cancer treatment.
Part of the book: Gene Expression and Regulation in Mammalian Cells
Distinct E2F-Mediated Transcriptional Mechanisms in Cell Proliferation, Endoreplication and Apoptosis
E2F and DP family proteins are evolutionally conserved transcription factors among higher eukaryotes. E2F and DP proteins typically form a heterodimeric complex, which controls cell proliferation by regulating expression of growth-related genes. In addition, E2F family proteins have roles in various cellular events that require the expression of context-specific genes. E2F proteins use distinct mechanisms to regulate context-specific genes in different circumstances. The primary goal of this chapter is to compare three distinct mechanisms of mammalian E2F-mediated transcriptional regulation that control cell proliferation, endoreplication and apoptosis. Briefly, E2F7 and E2F8 control endoreplication by suppressing the expression of their target genes. They do not require DP or pRb. In control of apoptosis, E2F1 regulates the expression of the tumor suppressor gene Arf by binding to a non-canonical E2F binding site, within the Arf promoter, in a DP-independent manner. Furthermore, we examine the functions of E2F and DP in Drosophila melanogaster (fruit fly) to identify those mechanisms of E2F-mediated transcriptional regulation that have been evolutionarily conserved. The detailed mechanisms of how E2F protein regulates the expression of context-specific target genes will be instrumental in understanding how a single family of transcription factor regulates diverse pleiotropic cellular processes in an organism.
Part of the book: Gene Regulation