CDK regulation and cyclin degradation

What does CDK regulation ensure?

The cell cycle proceeds in one direction only

Why do CDKs require regulation?

To prevent inappropriate or premature cell cycle transitions

What are the three key mechanisms regulating CDKs?

Cyclin binding

Which residues on CDK1 receive regulatory phosphates?

T14

Which residues inhibit CDK1 when phosphorylated?

T14 and Y15

Which kinase phosphorylates CDK1 on T14/Y15?

Wee1 kinase

What is the role of Wee1?

To place inhibitory phosphates on CDK1 or CDK2 during G2 to keep them inactive

What happens when Wee1 is active?

CDK1 remains inactive despite being bound to cyclin

Which kinase removes inhibitory phosphates?

Cdc25 phosphatase

What activates CDK1 at the G2/M boundary?

Cdc25C removing T14/Y15 phosphates

Is CAK activating or inhibitory?

Activating

Which residue does CAK phosphorylate?

T161

What is the role of CAK?

Adds activating phosphate to CDKs preparing them for full activation

Why is the CAK-modified CDK still inactive?

Because T14/Y15 inhibitory phosphates remain

What activates Cdc25?

Positive feedback from active CDK1 and other mitotic kinases

What happens once Cdc25 activates CDK1?

CDK1 activates more Cdc25 and inhibits Wee1

Why is CDK activation described as bistable?

Cells commit fully to mitosis rather than progressing gradually

What is a CKI?

Cyclin-dependent kinase inhibitor

Do CKIs block CDK activation?

Yes

Name a mammalian CKI that blocks G1 CDKs

p21 or p27 (any correct)

What removes CKIs in late G1?

Ubiquitin-mediated degradation

Why is multicellular control important?

Ensures CDKs respond to growth signals and DNA integrity

Why are multiple kinases used for regulation?

To integrate environmental inputs and checkpoints

Why is G2/M activation switch-like?

To ensure mitosis commits once entry is triggered

What is the APC/C?

An E3 ubiquitin ligase that targets cyclins for degradation

Which phase activates APC/C?

At metaphase-to-anaphase transition

What does APC/C target?

Cyclin A and Cyclin B

Why degrade cyclins?

To inactivate CDKs and exit mitosis

Which APC/C activator targets mitotic cyclins?

APC/C-Cdh1 and APC/C-Cdc20

Which APC/C activator functions first?

Cdc20 activates APC/C in metaphase

Which APC/C activator maintains cyclin degradation later?

Cdh1 form keeps CDK activity low in G1

Which enzyme system actually destroys cyclins?

Proteasome after polyubiquitination

What happens if APC/C fails?

Cyclin B persists

What checkpoint regulates APC/C activation?

Spindle assembly checkpoint

What happens when chromosomes are not properly attached?

Spindle checkpoint inhibits APC/C-Cdc20

What protein senses incorrect kinetochore tension?

The Mad/Bub checkpoint proteins

What happens if Wee1 is inhibited too early?

Cells enter mitosis prematurely and may die

What happens if Cdc25 is inhibited?

Cells arrest at G2/M boundary

Which protein regulates Wee1 activity?

Active CDK1 phosphorylates and inhibits Wee1

Which protein stimulates Cdc25?

Active CDK1 phosphorylates Cdc25 to further activate it

What type of feedback loop exists at G2/M?

Positive feedback loop (Cdc25 activation + Wee1 inhibition)

How do changes in phosphorylation affect CDK activity?

They turn complexes on or off rapidly

Why is phosphorylation reversible?

So cells can respond dynamically to internal conditions

What ensures G1 CDK activity remains low?

Active CKIs and APC/C prevent cyclin accumulation

What allows G1 to S transition?

Degradation of CKIs and accumulation of cyclin E/A

What is the role of growth factors in CDK regulation?

They induce cyclin gene expression (e.g.

What is the restriction point relative to CDK regulation?

Checkpoint where cell commits once Cyclin D/E CDKs overcome CKIs

What happens to CDK2 after restriction?

Becomes independent of mitogen signals

Which CDK becomes fully mitogen-independent?

CDK2 after Cyclin E accumulation

Why does CDK1 require Cyclin A first?

Cyclin A primes CDK1 before Cyclin B dominates mitosis

Which process starts when Cyclin A/CDK2 activity declines?

Cyclin B/CDK1 drives mitotic entry

How is Cyclin A destroyed?

By APC/C before Cyclin B

Which protein maintains mitotic exit?

APC/C inhibits CDK1 by degrading Cyclin B

What is the final CDK activity state after mitosis?

Very low or none

Why must CDKs reset?

To re-license DNA replication origins and start a new cycle

How do cells ensure phosphorylation events are ordered?

Sequential cyclin appearance and destruction

Why would simultaneous activation of all CDKs be dangerous?

Cells would replicate DNA and divide at the same time

Which organelle responds to CDK activity?

Nucleus (nuclear envelope breakdown) and centrosomes

What does CDK1 phosphorylate in prophase?

Nuclear lamins

Why must CDK1 activity fall before cytokinesis?

To allow chromosome decondensation and spindle disassembly

How do cells delay mitosis if DNA is damaged?

ATM/ATR pathways inhibit Cdc25 and activate Wee1

What happens if DNA damage repair fails?

Cell cycle arrest or apoptosis

Which biochemical system reverses phosphorylation?

Protein phosphatases

Name one CDK-dependent phosphatase

Cdc14 in yeast (anaphase)

What does Cdc14 do?

Releases phosphatase activity that resets CDK-driven phosphorylation

Why is CDK downregulation required for cytokinesis?

Actomyosin ring assembly requires dephosphorylated environment

What happens if phosphatases are inactive?

Cells fail mitotic exit and remain in a mitotic-like state

How is cell fate tied to CDK regulation?

Errors cause senescence