Regulation of the Cell Cycle Lecture 4 Flashcards

1
Q

All animal growth is based on _____ ____ or an increase in ____ _____ activity.

A
  • Cell proliferation

- cell cycle

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2
Q

How is cell growth initiated?

A

By the binding of an extracellular ligand, or growth factor, to a membrane receptor and the activation of kinases that increase gene expression

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3
Q

What is each phase of the cell cycle? Give a brief definition.

A
  • M Phase: Cell division
  • G1 Phase: RNA and protein synthesis and major regulatory events
  • G0: Resting cells
  • S: DNA replication and synthesis
  • G2: RNA and protein synthesis, mitotic spindle assembly
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4
Q

What regulates progression through the cell cycle? What mediates these?

A
  • Biochemical reactions, or checkpoints

- Checkpoints are mediated by kinases

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5
Q

Kinases that function as cell cycle checkpoints are composed of what two proteins? Which is the regulatory and which is the catalytic component?

A
  1. Cyclin Dependent Kinase (CDK) (Catalytic)

2. Cyclin (Regulatory)

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6
Q

True or False: CDKs without cyclin are unable to function as a kinase and have no catalytic activity.

A

True

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7
Q

How are cyclin:CDK complexes regulated?

A

-The genes that encode cyclins are only expressed during specific phases of the cell cycle, and cyclins rapidly degrade after completing their function

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8
Q

What do cyclin:CKD complexes do?

A

They phosphorylate protein substates in specific phases of the cell cycle, changing the proteins conformation and facilitating progression through the cell cycle. This can increase or decrease, or activate or inhibit, the function of a protein.

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9
Q

Cyclin D is an example of a ____ _____, so proteins encoded by Cyclin D perform similar functions in the body

A

Gene Family

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10
Q

What doe CyclinD/CDK4/6 and CylinE/CDK2 kinases do?

A

Phosphorylate and inactivate the retinoblastoma protein (Rb), which must occur for the cell cycle to continue

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11
Q

Rb is active when it is or is not phosphorylated? What does it do when it is active?

A
  • Is not phosphorylated

- Blocks progression of the cell cycle. It is the original tumor suppressor gene.

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12
Q

How does Rb (retinoblastoma protein) control cell cycle progression?

A

It binds to E2F. E2F is a transcription factor that binds to DNA at the E2 DNA recognition site, which is in promotor regions of genes that encode proteins that function in G1/S phase cell cycle progression and DNA synthesis in the S phase.

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13
Q

True or False: E2F is active when bound to Rb.

A

False, it is active when unbound from Rb

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14
Q

Unphosphorylated Rb is (active/inactive) and in a complex with _____, which is (activated/inactivated). This occurs during what cell cycle phases?

A
  • Active
  • E2F
  • Inactivated
  • G0 and early/mid G1
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15
Q

During Mid/Late G1, cyclin D gene is expressed. What does this do?

A

-Cyclin D forms an active kinase complex with CDK4/6, which then phosphorylates Rb and inactivates it, causing E2F to be released. Free E2F activates the transcription of genes encoding proteins needed in late G1 and S phase.

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16
Q

How is the cell cycle stopped?

A

By cyclin dependent kinase inhibitors (CDKIs)

17
Q

What are the two kins of CDKI’s and what do they inhibit?

A
  • Ink Family (inhibitor of kinase) which inhibit cyclin D/CDK4/6
  • Cip/Kip family (cyclin inhibitor protein/kinase inhibitor protein) which inhibits CyclinD/CDK4/6 and Cylin E/CDK2
18
Q

Cyclin D gene transcription is induced by growth factor signaling through ____ and downstream signaling pathways. Cyclin D is expressed in ____ and plays a critical role in ___ –> ___ phase transition.

A
  • Ras
  • G1
  • G1 –> S
19
Q

_____ is a key accessory protein that relays growth promoting signals from RTKs to intracellular signaling pathways.

A

Ras

20
Q

What are three growth arrest signals that induce the expression of CDKIs?

A
  1. Soluble growth inhibitors
  2. Contact inhibition
  3. DNA damage
21
Q

True or False: CDKI’s are tumor suppressors.

A

True