PCL486H1 Lecture Notes - Lecture 4: Caspase, Apoptosis, Cyclin-Dependent Kinase

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26 Feb 2017
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E3 is important for the recognition of a specific protein moved to the proteasome and degraded. Dna quality is assessed at the g1 and g2 checkpoints: atm and atr phosphorylate the checkpoint kinases chk1 and chk2 . Inhibit cdc25 by phosphorylation preventing activation of cyclin-cdk complexes: blocked cell cycle progression through g1-s transition or g2-m transition. Chk2 activates the inhibitory kinase wee1 reinforces the inhibition of cdk1: maintains the cells in g2 phase. Chk2 inhibits plk1 and prevents thus the action of early mitotic events. Maintained at very low levels by mdm2 e3 ligase-ubiquitin-mediated proteasome degradation. Chk2 activates p53 by phosphorylation releases it from mdm2 binding p53 will accumulate. P53 delays cell cycle progression in the g1 phase by stimulating the production of p21 (cip1) Inhibits cyclin d-cdk4/6 complexes, and cyclin e-cdk2 complexes. P53 is able to induce apoptosis transcription of bh3-only pro-apoptotic proteins puma and noxa. P53 also increase transcription of p14arf- mdm2 inhibitor allowing increase of p53 accumulation.

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