Tumor Initiating Cells, Cell Cycle Control and Cancer Stem Cells
Tumor Initiating Cells, Cell Cycle Control and Cancer Stem Cells
Tumor Initiating Cells, Cell Cycle Control and Cancer Stem Cells
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Summary<br />
1. D type cyclins respond to extra cellular signals to induce Rb phosphorylation<br />
<strong>and</strong> transition through the R point.<br />
2. Other cyclins (E, A, B) act autonomously to drive S phase <strong>and</strong> mitosis.<br />
3. CDK inhibitors p21 <strong>and</strong> p27 are required to assemble D-CDK4/6 <strong>and</strong> inhibit cyclins E, A<br />
<strong>and</strong> B-CDK complexes.<br />
4. As D cyclins become elevated they phosphorylate pRb (catalytic) <strong>and</strong> also sequester p21/p27<br />
(non-catalytic), thereby allowing E-CDK2 to further phosphorylate <strong>and</strong> inactivate pRb.<br />
5. Cyclin D1 also act as a transcriptional co-factor to induce or suppress transcription of various<br />
genes such as Notch1 during retinal development (non-Catalytic),<br />
6. Cyclin A <strong>and</strong> B maintain hyper-phosphorylated ppRb through S <strong>and</strong> G2/M. At mid-mitosis<br />
pRb is dephosphorylated by type 1 phosphatase.<br />
7. The pathways that regulate CDKI, the cyclins <strong>and</strong> associated kinases are often<br />
deregulated in human cancer.<br />
8. Rb-E2F suppress both cell cycle genes (cyclin E, Thymidylate synthase, Cdk1) as well<br />
as pro-apoptotic genes such as caspases, Puma, <strong>and</strong> Noxa. The effect of pRb-E2F<br />
deregulation (cell proliferation vs apoptosis) is context dependent.
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