23. Describe the p53 pathway in a few sentences and draw a flow diagram that goe

Question

23. Describe the p53 pathway in a few sentences and draw a flow diagram that goes along with your description to make sure that you include all of the following words in your description. (14 pts) Cross out each word as you proceed. P53, DNA binding site, recruits, TFIID, RNA PolII, p21, MDM2, Noxa, Puma, Cyclin Dependent Kinase, CDK inhibitor, RB, Phosphorylation, E2F, transcription factor, sequesters, release, G1 phase, S phase, cell cycle arrest, apoptosis, E3 ubiquitin ligase, degradation, stabilized, DNA damage, DNA Dependent Protein Kinase.

Explanation / Answer

p53 is a tumor suppressor protein encoded in humans by the TP53 gene. It is a crucial component in multicellular organisms, as it regulates the cell cycle and helps prevent cancer. p53 is the most frequently altered gene in human cancers. The name is due to its molecular mass: it is in the 53 kilodalton fraction of cell proteins.

p53 has many mechanisms of anticancer function, and plays a major role in inhibition of angiogenesis. As an anti-cancer promotion agent, it can activate DNA repair proteins when DNA has sustained damage, induce growth arrest by holding the cell cycle at the G1/S regulation point on DNA damage recognition, or initiate apoptosis if DNA damage proves to be irreparable. This is done by binding to the DNA.

p53 is maintained at low protein levels during times of homeostasis, when the cell is not exposed to stress or DNA-damaging events, by its predominant negative regulator Mdm2 through the ubiquitin-proteasome pathway. The Mdm2 E3 ubiquitin ligase represses p53 protein levels through continuous ubiquitination and degradation. The Mdm2-p53 interaction is inhibited by stress-induced acetylation and phosphorylation on Mdm2 by the kinases ATM and c-Abl. A number of phosphorylationand acetylation sites on p53 have been described and many serve to disrupt the Mdm2-p53 interaction as well. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis. Activated p53 binds DNA and activates expression of several genes including WAF1/CIP1 encoding for p21. p21 (WAF1) binds to the G1-S/CDK (CDK2) and S/CDK complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity. When p21(WAF1) forms a complex with CDK2 the cell cannot continue to the next stage of cell division. A mutant p53 will no longer bind DNA in an effective way, and, as a consequence, the p21 protein will not be available to act as the "stop signal" for cell division.

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