L16 role of ubiquitin proteasome system

What is the role of the ubiquitin

proteasome system in cell cycle regulation?

Which three enzymes are required for ubiquitination?

E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase)

How does E1 enzyme function in ubiquitination?

E1 activates ubiquitin and forms a covalent bond with it in an ATP

How does E2 enzyme function in ubiquitination?

E1 transfers ubiquitin to E2, covalently attaching Ub to E2

What is the role of E3 ubiquitin ligase?

E3 binds both the ubiquitinated E2 and the target protein to transfer ubiquitin to the substrate

What happens to a substrate once it is polyubiquitinated?

It is recognized by the proteasome and degraded, permanently inactivating it

Which ubiquitin ligase regulates G1 phase cyclin levels?

APC

What is the function of APC

Cdh1 in G1?

Which ubiquitin ligase regulates S

phase events?

What is the role of SCF during S

phase?

Which ubiquitin ligase regulates G2

M transition?

How does APC

Cdc20 regulate mitosis?

What regulates the switch from APC

Cdh1 to SCF at the G1/S transition?

How does CDK activity promote SCF activation?

By phosphorylating and triggering degradation of CDK inhibitors like p27 and the APC

Why is destruction of Cdh1 important at the G1/S transition?

It allows S

How does SCF contribute to directionality of the cell cycle?

By degrading phosphorylated proteins like Cdh1 and p27, ensuring CDK activity increases irreversibly

What is the role of Sic1 or p27 in G1 phase?

They inhibit S

How is Sic1/p27 degraded?

Phosphorylated by G1/S CDKs, then polyubiquitinated by SCF and degraded by the proteasome

What prevents DNA replication licensing outside of G1 phase?

High CDK activity phosphorylates licensing factors (Cdt1, Cdc6, ORC), which are then degraded by SCF

Which protein complex recognizes replication origins?

ORC (Origin Recognition Complex)

What happens to Cdt1 during S

phase?

What is MPF and how is it formed?

MPF is mitosis

How is MPF activated only at the G2/M transition?

Through opposing actions of Wee1 kinase (inhibitory) and Cdc25 phosphatase (activating)

How does MPF promote mitotic entry?

By phosphorylating substrates that drive chromosome condensation, spindle formation, and other mitotic events

Which protein complex ensures sister chromatids remain together after DNA replication?

Cohesin complex

How is cohesin removed during anaphase?

APC

What is the role of securin in mitosis?

Securin inhibits separase to prevent premature sister chromatid separation

How does APC

Cdc20 regulate metaphase

How does MPF regulate its own destruction?

MPF activates APC

What ensures irreversible G1/S transition?

Degradation of CDK inhibitors (p27/Sic1) and Cdh1 by SCF, increasing CDK activity

Which cyclins accumulate due to Cdh1 degradation at G1/S?

S

How does SCF prevent DNA re

replication?

What is the relationship between CDK activity and ubiquitin ligase activity?

CDK activity phosphorylates targets and ligase subunits, controlling timing of protein degradation

Which checkpoint ensures all chromosomes are properly attached to the spindle before anaphase?

Metaphase checkpoint

How is the metaphase checkpoint enforced?

Unattached kinetochores generate inhibitory signals that keep APC inactive until all chromosomes are aligned

What is the sequence of events for sister chromatid separation?

1. APC

Why is proteasomal degradation important for unidirectional cell cycle progression?

It permanently inactivates proteins like cyclins, CDKIs, and cohesin regulators to prevent reversal of transitions

Which ubiquitin ligase maintains low CDK activity in early G1?

APC

How does APC

Cdh1 inactivation contribute to S

Which ubiquitin ligase mediates the G2/M transition?

APC

Which proteins are degraded by APC

Cdc20 during mitosis?

How does MPF link G2/M transition and metaphase

anaphase transition?