339 Cyclins, CDKs, and p53

Which cyclins and Cdks are associated with which checkpoint?

Answer explanation

G1 - G1-cyclin + Cdk4/6

G1/S - G1/S cyclin + Cdk2

S - S-cyclin + Cdk2

M - M-cyclin + Cdk1

Are either Cdks or cyclins present in the cell at a constant level?

What is Wee1s’ role in the cell cycle?

Answer explanation

Wee1 is a kinase that phosphorylates inhibitory sites on the M-Cdk complex preventing progression through the cell cycle until the nutritional needs of the cell are met to ensure successful cell division

Describe M-Cdk within a positive feedback loop in the cell cycle

Answer explanation

M-cdk is involved in a positive feedback loop with Wee1 and cdc25. When M-Cdk is activated via cdc25, it signals to both cdc25 to continue is phosphatase activity on M-Cdk alongside inhibiting Wee1 from phosphorylating inactivating phosphorylating sites on M-Cdk.

Explain the inhibitory function of CKIs using examples

Answer explanation

CKIs inhibit cyclin-cdk complexes by binding to them and . An example includes p27 with the G1/S complex, inhibiting it from progressing the cell cycle when growth factors are present indicating the cell needs to grow, or prevent replication.

What is the role of SCF?

Answer explanation

SCF is a complex involving 3 proteins: Skp, cullin, and F-box. It is involved in regulating the amount of Cyclins and CKIs within the cycle via ubiquitination.

How does the APC/C contribute to the cell cycle?

Answer explanation

The anaphase-promoting complex c encourages the progression from metaphase to anaphase by ubiquitinating the M-Cyclin, thereby targeting it to be degraded within the proteasome. This is initiated by Cdc20 which is controlled by M-Cdk complex and the spindle assembly checkpoint (SAC) proteins.

Explain the interaction between Rb and E2F

What is Myc responsible for?

Answer explanation

Myc is gene regulatory signal that is reponsible for the transcription of genes that promote cell growth by inhibiting passage through the cell cycle such as E2F.

Describe the roles of p53 in the cell cycle

Answer explanation

p53 is a tumor supressor, it halts the progression through the cell cycle at the G1/S phase checkpoint to allow for DNA damage to be repaired. It does this by activating the transcription of p21, a PKI that binds to G1/S cyclin cdk complex. If the damage is unrepairable, then it will initiate apoptosis via the Bax gene.