University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

343

Pages:

1
Author:

Mariam A. A.

Cell Cycle Regulation Summary Growth Factors (GF): VEGF, EGF, PDGF act as mitogens, stimulating the cell cycle. Signal Transduction Pathways: Activation of PI3K triggers downstream signaling (e.g., activation of AKT). PIP2 gets converted to IP3 and DAG, which further propagate the signal. IP3 promotes the release of Ca²⁺ from storage, while DAG activates PKC, leading to phosphorylation of target proteins. Ca²⁺ Signaling: Calcium ions bind to calmodulin, forming a complex that activates various kinases. These kinases can promote cellular activities like proliferation. Cyclins and CDKs: Cyclins (e.g., Cyclin A, D, E) bind to CDKs (Cyclin-Dependent Kinases), forming active complexes that drive the cell cycle forward. Cyclins control progression through the cell cycle phases (G1, S, G2, M). Rb protein controls the G1 checkpoint by binding transcription factors like E2F. Hyperphosphorylation of Rb releases E2F, promoting progression into S phase. Tumor Suppressors and Proto-oncogenes: p53 acts as a guardian of the genome, halting the cell cycle in response to DNA damage. Mutations in p53 or ATM can lead to unregulated cell proliferation. RAS (proto-oncogene) activation promotes cell division but must be tightly controlled. Checkpoints: Ensure proper cell cycle progression and integrity. G1/S Checkpoint: DNA integrity is checked before replication. G2/M Checkpoint: Ensures all DNA is replicated and undamaged before mitosis. M Checkpoint: Checks for proper chromosome attachment to the spindle before anaphase. Cell Cycle Inhibition: Proteins like BAX promote apoptosis in response to severe DNA damage. p21, p27 inhibit CDKs, preventing the cell cycle from proceeding under unfavorable conditions. Anaphase-Promoting Complex (APC): Facilitates progression through mitosis by tagging proteins like securin for degradation, allowing separase to cleave cohesins and separate sister chromatids.