CyclinD Flashcards

1
Q

Which Cyclin forms active complexes with CDK4 and CDK6 during the G1 phase?

A

Cyclin D

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2
Q

What is the function of Cyclin D-CDK4/6 complexes in the G1 phase?

A

They phosphorylate the retinoblastoma protein (Rb).

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3
Q

What effect does hypophosphorylated Rb have on E2F transcription factors?

A

It binds to them, preventing the initiation of gene transcription required for S phase entry.

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4
Q

What happens to Rb when phosphorylated by Cyclin D-CDK4/6?

A

It becomes inactivated, releasing E2F.

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5
Q

What is the role of E2F after its release from Rb?

A

It promotes the transcription of genes necessary for DNA replication.

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6
Q

What critical checkpoint must a cell pass to commit to entering the S phase?

A

The restriction point (R-Point).

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7
Q

Which complexes are crucial for a cell to pass the restriction point in late G1?

A

Cyclin D-CDK4/6 complexes.

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8
Q

What phase does the cell enter after passing the restriction point?

A

The S phase.

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9
Q

How does phosphorylation affect the retinoblastoma protein (Rb)?

A

It inactivates Rb, allowing the cell cycle to progress.

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10
Q

What is the consequence of E2F being released from Rb in the cell cycle?

A

It initiates the transcription of genes required for DNA replication.

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11
Q

What determines if a cell commits to DNA replication regardless of external signals?

A

Passing the restriction point (R-Point) in late G1.

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12
Q

What prevents E2F from initiating S phase gene transcription when bound to it?

A

Hypophosphorylated retinoblastoma protein (Rb).

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13
Q

What is the main function of Cyclin D in cell cycle regulation?

A

To partner with CDK4 and CDK6 to phosphorylate Rb, facilitating the G1/S transition.

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14
Q

What is the role of Cyclin D-CDK4/6 complexes in the G1 phase?

A

They phosphorylate the retinoblastoma protein (Rb), promoting the G1/S transition.

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15
Q

What happens to retinoblastoma protein (Rb) when phosphorylated by Cyclin D-CDK4/6?

A

It becomes inactivated, releasing E2F transcription factors.

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16
Q

What is the consequence of E2F release during the G1 phase?

A

E2F promotes the transcription of genes required for S phase entry.

17
Q

How does Rb protein regulate the G1/S transition before phosphorylation?

A

It binds to E2F, preventing transcription of S phase genes.

18
Q

What is the Restriction Point (R-Point) in the cell cycle?

A

A checkpoint in late G1 where the cell commits to entering the S phase.

19
Q

What is the significance of passing the Restriction Point in the G1 phase?

A

The cell commits to DNA replication, regardless of external signals.

20
Q

How do Cyclin D-CDK4/6 complexes influence the Restriction Point?

A

Their activity is crucial for passing the Restriction Point.

21
Q

What does hypophosphorylated Rb do?

A

Binds to E2F, inhibiting the transcription of genes required for S phase.

22
Q

What marks the commitment to the S phase?

A

The cell passing the Restriction Point.

23
Q

What phase of the cell cycle is regulated by Cyclin D-CDK4/6 activity?

A

The G1 phase.

24
Q

Which transcription factors are released upon Rb phosphorylation?

A

E2F transcription factors.

25
Why is Cyclin D important in the cell cycle?
It partners with CDK4/6 to regulate the G1/S transition.
26
What triggers the inactivation of Rb protein?
Phosphorylation by Cyclin D-CDK4/6 complexes.
27
What is the clinical significance of dysregulation of Cyclin D in oncogenesis?
It leads to uncontrolled cell proliferation due to aberrant activation of CDK4/6, observed in various cancers.
28
In which cancer is Cyclin D1 overexpression particularly associated?
Mantle cell lymphoma.
29
What role does Cyclin D1 play in cancer development?
It acts as an oncogene, promoting tumorigenesis by overriding normal cell cycle controls.
30
How is Cyclin D1 overexpression linked to breast cancer?
It contributes to tumorigenesis by driving cell proliferation.
31
What is the therapeutic approach targeting Cyclin D-CDK4/6 complexes in cancer treatment?
Use of specific inhibitors like palbociclib, ribociclib, and abemaciclib.
32
Which cancers are CDK4/6 inhibitors particularly effective against?
Hormone receptor-positive breast cancer.
33
How do CDK4/6 inhibitors work?
They block the kinase activity of CDK4/6, leading to cell cycle arrest in G1 phase.
34
Name a mechanism by which cancer cells develop resistance to CDK4/6 inhibitors.
Upregulation of Cyclin E-CDK2 activity.
35
What is another mechanism of resistance to CDK4/6 inhibitors?
Loss of Rb function.
36
How does overexpression of CDK6 contribute to resistance to CDK4/6 inhibitors?
It bypasses the inhibition and allows cell cycle progression.
37
Why is Cyclin D1 overexpression a significant marker in esophageal cancer?
It indicates a higher likelihood of aggressive tumor behavior.
38
What is a common outcome of gene amplification involving Cyclin D1 in cancers?
Increased cell cycle progression leading to tumor growth.
39
How does chromosomal translocation involving Cyclin D1 affect cancer development?
It can result in abnormal Cyclin D1 expression, driving oncogenesis.