The Cell Cycle The cell cycle is the series of tightly regulated steps that controls cell growth (phase G1, G2), DNA synthesis (S phase), and the gymnastics of DNA segregation and cytokinesis (M phase). Control flux through the cell cycle arrises from interplay between the Cyclins and their Cyclin-dependent kinases (CDKs), promoting the cell cycle, and the tumor suppressors (the transcription factor (regulators) Retinoblastoma (Rb) and p53 shown here) which prevent progression through the cell cycle. Cancer, in simplest terms, is unregulated cell proliferation. Both Rb and p53 serve as stop-gaps to unregulated cell proliferation by inhibiting the transcription factor E2F (in the case of Rb), preventing progression through the G1/S checkpoint, or directly acting as a transcription factor (in the case of p53), preventing progression through the G1/S, S/G2, G2/M checkpoints. Did you notice how much p53 seems to be doing? Thats right, p53 regulates 3 out of 4 of the cell cycle checkpoints, including the important task of responding to and repairing damaged DNA. When the cell senses damaged DNA, p53 is activated, halting the cell cycle and upregulating enzymes that repair damaged DNA. If, however, the task is too great, p53 will initiate a programed cell death pathway to protect the organism from a potential cancer cell. It should be no surprise then that p53 is found to be mutated in over 50% of cancers. While taking place at the cellular level, you’ve probably experienced this yourself. Ever had bad sunburn? Yes, its p53 (and a host of other proteins) that cause your top layer of skin to dye and peel off. Yuck! But it’s not just us who rely on p53. The famously long lived elephant has 40 copies of the p53 gene (TP53) to our measly 2, and researchers currently believe that may be one reason why an elephants lifetime risk of cancer is <5% compared to our +30% risk (although finding MRIs big enough for an elephant is a tad bit tricky). #cell #cycle #p53 #Cyclins #Cyclin-dependent kinase #CDK #tumor suppressor #transcription factor #Rb #Retinoblastoma #tp53 #cell cycle #Cancer #proliferation #TF #E2F #checkpoint #DNA #cell death
