Actually Cell Cycle this time Quiz

Cell Cycle Regulation in Mitosis

• The M-Cdk complex is inhibited via phosphorylation by Wee1 and de-phosphorylated by Cdc25 to initiate mitosis.
• The M-Cdk complex is essential for the activation of proteins required for mitosis, which progresses through prophase, pro-metaphase, and metaphase.
• The Metaphase-to-Anaphase (M-to-A) checkpoint is regulated by the APC/C complex, which targets securin for destruction to allow sister chromatid separation.
• After anaphase, the M-cyclins are targeted for destruction, leading to dephosphorylation of Cdk targets required for the completion of mitosis.
• Unfavorable conditions can pause the cell cycle at key checkpoints, such as G1, S, and the M-to-A checkpoint.
• The cell cycle progression can be regulated by Cdk inhibitory proteins (CKIs) and tumor suppressor genes, such as p16, p21, p27, p53, and RB.
• CKIs primarily govern the activities of G1/S and S-Cdks early in the cell cycle, inhibiting cyclin-Cdk complexes.
• Tumor suppressor genes p53 and RB play crucial roles in recognizing damaged DNA and promoting cell cycle arrest.
• Contact inhibition, regulated by cadherins and the Beta-catenin pathway, can also inhibit cell cycle progression by preventing cell division when in contact with other cells or matrix components.
• Extracellular signaling can either promote cell proliferation or inhibit the cell cycle through survival pathways.
• The regulation of the cell cycle involves complex molecular mechanisms, including the activation and inhibition of cyclin-Cdk complexes and the recognition of DNA damage.
• Understanding the molecular basis of cell cycle regulation is crucial for comprehending the complex mechanisms that govern cell division and proliferation.

Cyclin-Cdk Complexes in Cell Cycle Regulation

• There are 4 classes of cyclins that form specific complexes with Cdks: G1/S-cyclins, S-cyclins, M-cyclins, and G1-cyclins.
• Cyclin-Cdk complexes play a crucial role in cell cycle regulation by triggering progression through different checkpoints such as the G1/S checkpoint and the G2/M checkpoint.
• Cyclin E forms a complex with Cdk2 at the end of G1 and helps trigger progression through the start transition, while Cyclin A forms a complex with Cdk1 and Cdk2 to stimulate chromosome duplication during S phase.
• The accessibility of Cdk substrates changes during the cell cycle, leading to different effects induced by cyclin-Cdk complexes at different times.
• The anaphase promoting complex (APC/C) is needed for the progression through the Metaphase-to-anaphase checkpoint and stimulates the proteolytic destruction of specific regulatory proteins.
• Growth factors are required in the G1 phase to stimulate cellular growth and proliferation, leading to the transcription and translation of Cyclin D and Cyclin E.
• The G1-cdk complex, formed by Cyclin D and Cdk4/Cdk6, and the G1/S-cdk complex, formed by Cyclin E and Cdk2, allow progression through the start checkpoint by targeting the protein RB and phosphorylating it.
• Hyperphosphorylation of RB inactivates it, releasing a transcription factor E2F and allowing transcription to proceed, including the transcription of cyclin E and cyclin A.
• Cyclin D and Cyclin E are targeted for destruction by a protein called SCF in early S phase, promoting progression through the S phase of the cell cycle.
• The S-cdk complex allows progression through the S phase, while the M-cyclin levels begin to rise in G2 phase, forming the M-Cdk complex needed to pass through the G2/M checkpoint.
• The M-Cdk complex is controlled to ensure that mitosis doesn’t start too soon, with the M-cyclins transcribed at specific times and targeted for proteolysis by APC/C at the end of G2.
• Cyclin-Cdk complexes function by activating the Cdk, directing it to a specific target protein, and inducing different effects at different times in the cell cycle due to changes in substrate accessibility.