Cell Cycle, Apoptosis and Cancer Flashcards

1
Q

What are the stages of the cell cycle?

A

Mitosis- nuclear division
Interphase- G1, S and G2
G0 phase- withdraw from cell cycle

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2
Q

What is G1 phase>

A

Gap 1 phase- RNA and protein synthesis needed for DNA replication

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3
Q

What is the S phase?

A

Phase of DNA synthesis

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4
Q

What is G2 phase?

A

Gap 2 phase- DNA stability is checked

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5
Q

Restriction point

A

Occurs in G1- Cell must receive growth factors to move past restriction point. Occurs about 2 hours prior to S phase.

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6
Q

G1 checkpoint

A

occurs around the same time of restriction point- Occurs in response to DNA damage before replication

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7
Q

G2 checkpoint

A

Verify the completion of genomic duplication

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8
Q

Metaphase checkpoint

A

Ensures that the chromosomes are attached to mitotic spindles for proper separation

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9
Q

Cell proliferation

A

Myc-TF will increase gene expression of G1 cyclin dependent kinase- CDK then phosphorylates retinoblastoma, releasing the E2F protein.

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10
Q

What is the factor that drives G1 to S phase?

A

The release of E2F from phosphorylated Rb will begin s phase gene transcription

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11
Q

What genes do E2F stimulate?

A

Transcription of Cyclin E and Cyclin A which activates CDK2

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12
Q

Feedback of cell proliferation

A

Cyclin E-CDK2 and Cyclin A-CDK2 keep Rb in hyperphosphorylated state. Transcription of genes also create a positive feedback loop

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13
Q

Activation of cyclin-CDK activity

A

Cyclin binds to CDK which partial activates the t loop but full activation requires CDK-activating Kinase to phorphorylate the t-loop

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14
Q

What cyclin-CDK complexes get past restriction point?

A

Cyclin D- CDK4 and Cyclin D-CDK6

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15
Q

Inhibition of cyclin-CDK activity

A

Wee1 kinase inhibits by phosphorylating “roof site” of complex
p27 will bind to both cyclin and CDK to inactivate the complex

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16
Q

What is the function of cdc25 phosphatase?

A

It will dephosphorylate roof site after Wee1 inactivates CDK complex

17
Q

What is APC/C?

A

Anaphase-promoting complex- a member of the ubiquitin ligase family. it regulates the progression from metaphase to anaphase.

18
Q

What is ubiquitin?

A

a small protein that is attached to the lysine residues of proteins to signal destruction of the protein

19
Q

How does the cell cycle move into anaphase?

A

CDC20 will activate APC/C leads to the addition of polyubiquitin to S and M cyclins. The destruction of cyclins inactivates the CDK and allows for progression into anaphase.

20
Q

what is p53?

A

The guardian of the genome- responds to DNA damage and will regulate transcription to halt cell cycle

21
Q

What is the process for activation of p53?

A

DNA damage will activate protein kinase. p53 will then be phosphorylated and begin transcription of genes for p21

22
Q

What is p21?

A

It is a cyclin-dependent kinase inhibitor (CKI) and will primarily inhibit CDK2

23
Q

What is the intrinsic pathway of apoptosis?

A

Mitochondrial dependent- responds to DNA damage, lack of O2, nutrients or extracellular survival signals

24
Q

What is the extrinsic pathway of apoptosis?

A

It is a mitochondrial independent cycle

25
Q

Capase activation

A

Capase are responsible for apoptosis. Activated by protease cleavage. Will make a heterodimer that forms from a small and a large subunit

26
Q

What are the two initiator proteins of apoptosis?

A

Capase 8 and capase 9

27
Q

What are the executioner proteins of apoptosis?

A

Destroys the targets and executes apoptosis. Ex is Capase 3, 6 and 7- They are activated by capase 8 and 9

28
Q

Describe the intrinsic pathway of apoptosis

A

Capase 8 is activated which will then stimulate BAX. BAX then aggregates in the mitochondrial membrane, releasing cytochrome C into the cytosol. Cyto C and hydrolysis of ATP activates Apaf1 creating an apoptosome. This then recruits and activates procapase 9 leading to the activation of executioner proteins.

29
Q

What is a proto-oncogene?

A

Growth factors, receptors of GFs, transcription factors and signal transducers- Most are involved in cell growth and division

30
Q

What is an oncogene?

A

a mutation in a proto-oncogene that results in increased expression of proteins and causes the cell to act abnormally. Most result in cancer mutations

31
Q

What is the HER2 gene?

A

Tyrosine Kinase Receptor. Mutation causes overexpression of HER2, seen in many breast cancers

32
Q

Tumor suppressor examples

A

RB1- causes retinoblastomas
TP53
PTEN- phosphatase and tensin homolog- prostate cancer
APC- Adenomatous polyposis coli- Colon cancer

33
Q

What is Herceptin?

A

An inhibitor of oncoproteins- HER2

34
Q

What is Gleevec?

A

An inhibitor of oncoproteins- BCR-ABL

35
Q

What is Erbitux?

A

An inhibitor of oncoproteins- EGF receptors