Understand the sequence of cyclin/cdk interactions through cell cycle progressio

Question

Understand the sequence of cyclin/cdk interactions through cell cycle progression Know how the G1 restriction point, G1 checkpoint, G2 checkpoint, and M (spindle) checkpoint function, what proteins and processes are coupled to these functions, and what may prevent the cell cycle from progressing through any of these restriction points or checkpoints Understand how cdk activities are regulated and how these activities are repressed by cyclin dependent kinase inhibitors Understand the concept of tumor suppressor genes; how they can become inactivated in cells; how 'recessive' mutants can function in an autosomal dominant manner (Rb, BRCA1 and BRCA2) or dominant negative (p53) manner Know the differences between inherited and somatic forms of tumor suppressor gene inactivation and how these contribute to tumorigenesis; what kinds of tumors are associated with each mode of inactivation? What are the ages of onset? Are mutations typically distributed throughout these genes or concentrated in specific 'hot spots? Understand Knudsen's Hypothesis and the concept of haploinsufficiency with regard to tumor suppressor gene inactivation and consequent tumorigenesis Know how Rb is regulated and how it, in turn, regulates progression through the cell cycle. Understand the role of Rb as a tumor suppressor gene, how it can cause inherited and somatic forms of retinoblastoma. Understand how p53 opposes movement through the G1 phase of the cell cycle, and how, in turn, p53 levels are regulated in the cell. Know how it functions as a transcription factor and what gene(s) it regulates, and how this function is disrupted if p53 is mutated. Know how the 3 major mutations alter p53 protein function. Understand the homotetramer structure of normal p53 and how this is altered if p53 is mutated What are the 'danger signals' that activate normal p53? How are these transmitted to the p53 protein? What are the anti-tumor activities of normal p53 and how are these accomplished? How does p53 mutation inhibit or ablate these anti-tumor activities? Understand how MDM2 and p53 regulate each others expression. How do Myc and Miz-1 teract with p53? What do these interactions accomplish? Why do p53, Myc, or ASPP mutations promote tumorigenesis? How do viruses disable normal Rb and p53 function and thereby promote progression through the cell cycle? Know and be able to explain the various therapeutic strategies focused on increasing normal p53 levels or disabling mutant p53 proteins in cancer cells.

Explanation / Answer

Different danger signals that activate normal p53 include cell stress and DNA damage. These are transmitted to p53 protein by upstream stress activators. These upstream stress activators include radiation-, drug-, or carcinogen-induced DNA damage, oncogenic activation, hypoxia, and low ribonucleotide pools. The stress activators affect cellular proteins, mostly kinases which further convey the danger signals to p53 via phosphorylation.

Reference: Molecular Biology of Cancer: Mechanisms, Targets, and Therapeutics by Lauren Pecorino

Related Questions

Navigate

• Browse (All)
• Browse U
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.