PRINCIPLES OF TOXICOLOGY - Biology East Borneo

13.4 MOLECULAR ASPECTS OF CARCINOGENESIS 285The Rb gene encodes a 107-kD nuclear protein that plays a critical role in the early stage of thecell cycle. When the cell is stimulated by a growth factor, that signal is ultimately relayed to the nucleus.This signal results in the production of proteins that temporarily inactivate Rb. In its active form, theRb protein is tightly bound to an important transcription factor, E2F. When the cell receives a signalto divide, Rb is hyperphosphorylated, causing a conformational change and the release of E2F. Thetranscription factor E2F induces the production of other proteins involved in cell cycle progression.The Cell Cycle and ApoptosisIt is important to discuss some of the processes that govern the life and death of cells to better understandhow oncogenes and tumor suppressor genes are involved in these processes. As pointed out previously,proto-oncogenes function in various capacities in the transduction of signals for cell growth anddifferentiation within and between cells. In normal cells, replication of the DNA and cell division isstimulated by the presence of growth factors that bind receptors at the cytoplasmic membrane andinitiate a cascade of intracellular signals. Once these signals reach the nucleus they cause thetranscription of a complex array of genes, producing proteins that mediate progression of the cellthrough the cell cycle culminating in mitosis or cell division.The cell cycle is divided into five phases (Figure 13.6). The length of each of these phases can varydepending on factors such as cell type and localized conditions within the tissue. After completingmitosis (M), daughter cells enter the Gap 1 (G 1) phase. If conditions are favorable, cells enter thesynthesis (S) phase of the cycle, where the entire genome of the cell is replicated during DNA synthesis.Following S phase, cells enter the Gap 2 (G 2) phase before proceeding through mitosis again. Thereis a critical boundary early in G 1called the restriction point. This is the point at which the cell mustFigure 13.6 Schematic diagram of the cell cycle including primary checkpoints.