ISCI 1A24 Lecture Notes - Lecture 8: Epistasis, Beta-Catenin, Mdm2

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One of first discovered tumour suppressors was responsible for retinoblastoma. Ras-mapk pathway if a growth factor is present, this pathway is initiated. Genes are transcribed to lead to enzymes and proteins required for s (synthesis) phase. Rb protein is usually attached to e2f and inactivated. When growth factor appears, rb protein is phosphorylated and e2f protein is free to facilitate gene transcription. Gatekeeper genes (signaling, ensuring readiness of dna for cell cycle) p53 (dna damage response), apc, pten, cdkn2a, rb. Caretaker genes (breakage and damage) brca1 and 2 (strand break repair) Role of p53 in response to dna damage: Normally, p53 is attached to mdm2 complex (enzyme) With damage, p53 is phosphorylated becomes unbound from mdm2 p53 transcribes puma factor (inhibits protein responsible for inhibition of apoptosis bc12, causes apoptosis), transcribes p21 (inhibits cdk, which then cannot phosphorylate rb arrests cell cycle)

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