CDKs and Cyclins

What type of kinase are CDKs?

Serine/threonine kinases

How many cyclin-dependent kinases are involved in mammalian cell cycle control?

Four

Which mammalian CDK pairs with Cyclin B?

CDK1

Which mammalian CDK pairs with Cyclin A?

CDK1 and CDK2

Which CDKs pair with Cyclin D?

CDK4 and CDK6

Which CDK pairs with Cyclin E?

CDK2

Which CDK drives entry into mitosis?

CDK1

Which CDK drives S-phase progression?

CDK2–Cyclin A

Which CDK drives G1 progression?

CDK4/6–Cyclin D

Which CDK drives the G1/S transition after the restriction point?

CDK2–Cyclin E

What does CDK stand for?

Cyclin-Dependent Kinase

Why are CDKs dependent on cyclins?

CDKs require cyclins to activate their kinase function

What are cyclins named for?

Their cyclical expression levels across cell cycle phases

At what point do cyclin levels change?

Cyclins accumulate gradually then are rapidly degraded

What enzyme system destroys cyclins?

Ubiquitin–proteasome system

Why is cyclin destruction important?

Prevents reversal and ensures unidirectional cell cycle progression

Are Cyclin D levels degraded like other cyclins?

Total Cyclin D levels remain relatively constant

How are nuclear Cyclin D levels regulated?

By controlled import and export

Which cyclin accumulates during G1?

Cyclin D

Which cyclin rises at the G1/S boundary?

Cyclin E

Which cyclin controls most of S phase?

Cyclin A

Which cyclin peaks at G2/M?

Cyclin B

Which CDK is homologous to yeast cdc28?

CDK1

Which CDK is homologous to pombe cdc2?

CDK1

How many CDKs exist in mammals in total?

At least nine

How many mammalian CDKs are strictly cell cycle related?

Four CDKs (CDK1

Which cyclins regulate G1 in mammalian cells?

Cyclin D family

Which cyclins regulate S phase?

Cyclin E and Cyclin A

Which cyclins regulate mitosis?

Cyclin A then Cyclin B

What happens to CDK activity if cyclins are absent?

CDKs remain inactive

Which cyclin binds first to CDK2?

Cyclin E

Which cyclin binds CDK2 after Cyclin E?

Cyclin A

Which cyclin is required for G2/M transition?

Cyclin B

Which cyclin is involved in early mitosis?

Cyclin B

Which single CDK drives all yeast cell cycle phases?

Cdc28

Which yeast cyclins act at START?

Cln1

Which yeast cyclins drive DNA replication?

Clb5 and Clb6

Which yeast cyclins function at G2/M?

Clb1-4

What type of regulation makes the same CDK do different jobs?

Partnering with distinct cyclins

How do cyclins determine CDK substrate choice?

Cyclins recruit specific substrates to CDKs

What motif recruits substrates to cyclins?

RXL motif

What is the purpose of RXL motifs?

Docking short sequences that allow substrate recognition

Why do different cyclins regulate different substrates?

Cyclins have different affinities and docking surfaces

Which cell cycle phase is influenced by cyclin accumulation?

All major checkpoints rely on cyclin accumulation

Which subunits compose MPF?

Cyclin and CDK1

Who discovered MPF activity?

Studies using sea urchin oocytes revealed it

What triggers MPF activation?

Cyclin B accumulation and CDK1 dephosphorylation

What does MPF cause?

Entry into mitosis

Where does Cyclin B accumulate before activation?

In the cytoplasm until nuclear envelope breakdown

What causes Cyclin B destruction?

Targeting by APC/C ubiquitin ligase

When is Cyclin B degraded?

During anaphase

What happens when Cyclin B is degraded?

CDK1 activity drops and mitotic exit begins

What keeps CDKs inactive even if cyclin is bound?

Inhibitory phosphorylation (e.g.

Which kinase adds inhibitory phosphates to CDK1?

Wee1

Which kinase activates CDK1 by priming it?

CAK phosphorylates T161 residue

Which phosphatase activates CDK1 fully?

Cdc25 removes the inhibitory phosphates

What is the restriction point?

Commitment step after which proliferation is cyclin-independent

Which complex controls the restriction point?

Cyclin D/CDK4/6 and later Cyclin E/CDK2

What is the key difference between START and the restriction point?

START is yeast equivalent of R point in mammals

Why does CDK4/6 activity rise early?

Because mitogens stimulate Cyclin D production

Why can Cyclin D levels fall quickly?

Cyclin D is mitogen-dependent and may be exported from the nucleus

Why is cyclin switching sequential?

Substrate preferences enforce correct ordering of cell cycle tasks

How does cyclin degradation enable order?

Later cyclins replace earlier ones and change CDK activity targets

What protein family restrains CDKs?

CKIs (cyclin-dependent kinase inhibitors)

What is an example of a CKI?

Sic1 in yeast; p21/p27 in mammals

How do CKIs interact with cyclin-CDK complexes?

They bind and block CDK catalytic activity

When must Sic1 be degraded?

Before S phase initiation

How is Sic1 targeted for degradation?

Phosphorylated by CDK and ubiquitinated

What happens if Sic1 persists?

Cell arrests in G1

How many phosphorylation events are usually needed to degrade CKIs?

Multiple (multisite phosphorylation)

Why do different cyclin-CDK pairs not function redundantly?

Each pair targets functionally distinct substrate sets

Why are multiple cyclins necessary?

Sequential activation ensures directionality and timing

What ensures mitosis only occurs once per cycle?

Cyclin A and B destruction resets CDK1

What ensures DNA replication only happens once?

Cyclin switching from E to A shuts down further licensing

Why is CDK1 essential?

It is the only CDK fully required for mitosis

Why do higher organisms use multiple CDKs?

Signal robustness and flexible regulatory points

Why do yeasts use one major CDK?

Cyclin choice alone can provide functional diversity