1. Cell cycle progression is counteracted by pRb (which inhibits the function of E2F), cyclin-dependent protein kinase inhibitors (such as p15, p16, and p21), p53 (that transactivates the p21 gene), and ARF (also called p14 that binds to mdm2, thereby neutralizing the antagonistic effect of mdm2 on p53). Signals evoked by DNA damage and TGF-β will ultimately result in accumulation of p53 and p15 proteins, respectively, and deceleration of the cell cycle. In contrast, mutations that disable the tumor-suppressor proteins facilitate cell-cycle progression and neoplastic conversion and are common in human tumors. Aflatoxin B1 (ATX), B P, and UV light cause such mutations of the p53 gene.
Source: Chapter 3. Mechanisms of Toxicity, Casarett & Doull's Essentials of Toxicology, 2e
Citation: Klaassen CD, Watkins JB, III. Casarett & Doull's Essentials of Toxicology, 2e; 2010 Available at: Accessed: November 12, 2017
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