Question

Which of the following statement(s) about p53 are true?

		p53 controls both the G2/M and the G1 cell cycle checkpoints
		The p53 tumor suppressor protein plays a key role in the regulation of the cell cycle and cell death
		All of the above
		p53 is tumor promoter protein
		p53 involves in the Ub mediated proteolysis pathway
		The p53 gene has a wide spectrum of mutations in human tumors
		None of the above

Answer 1

True

• p53 controls both the G2/M and the G1 cell cycle checkpoints

Increased expression of wild-type p53 in response to DNA damage arrests cells late in the G1 stage of the cell cycle by stimulating the synthesis of inhibitors of cyclin-dependent kinases, such as p21/WAF1. When p53 is expressed at a level comparable to that induced by DNA damage in other cells, most MDAH041 cells arrested in G1, but a significant fraction also arrested in G2/M. Cells released from a mimosine block early in S phase stopped predominantly in G2/M in the presence of p53, confirming that p53 can mediate arrest at this stage, as well as in G1. p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts.

• The p53 tumor suppressor protein plays a key role in the regulation of the cell cycle and cell death

The p53 tumor suppressor protein plays a key role in the regulation of the cell cycle and cell death. The p53 protein is also involved in cell differentiation, DNA repair, senescence and angiogenesis. Wild-type (wt) p53 and intact signaling pathways are essential for the prevention of cancer.

• The p53 gene has a wide spectrum of mutations in human tumors

The p53 gene has a wide spectrum of mutations in human tumors. The great majority of the mutations are clustered in the core domain (120–292 bp). This domain is important for DNA- specific binding and is essential for p53 function.

False

• p53 is tumor promoter protein

p53 is a tumor suppressor protein.

• p53 involves in the Ub mediated proteolysis pathway

The ubiquitin proteasome pathway is critical in restraining the activities of the p53 tumor suppressor. Numerous E3 and E4 ligases regulate p53 levels. Additionally, deubquitinating enzymes that modify p53 directly or indirectly also impact p53 function. When alterations of these proteins result in increased p53 activity, cells arrest in the cell cycle, senesce, or apoptose. On the other hand, alterations that result in decreased p53 levels yield tumor-prone phenotypes.