Chapter 21 - Regulation Of The Cell Cycle

Question 1

Cell cycle mediators are?

Answer 1

Cyclins or CDK’s

Question 2

What are the different cyclins for phases of cell growth?

Answer 2

• Cyclins D : Regulate G1 through the restriction point
• Cyclins E and A : proceed the cell through S phase
• Cyclins B and A : Mitotic cyclins

Question 3

How does the CDK-cyclin complex work?

Answer 3

• the complex stimulates the kinase activity of CDK
• CDK becomes phsophorylated and this active cyclin-CDK complex catalyzes the phosphorylation of serine and threonine aa residues
• the result is the change in state of substrate proteins which acauses the cell to progress towards the next phase

Question 4

Cell that temporarily or reversibly stop dividing are?

Answer 4

Quiescence cells

Question 5

What are senescent cells?

Answer 5

Cells that permanently stop dividibg, eith due to age or due to accumulated DNA damage

Question 6

Cyclins and CDK’s for different cell phases?

Answer 6

CDK4/CDK6 + Cyclin D -> progression past the “restriction point” at the G1/S boundary
CDK2 + Cyclin E/A -> initiation of DNA synthesis in early S phase
CDK1 + Cyclin B -> transition from G2 to M

Question 7

Tumor supressor proteins?

Answer 7

Proteins that normally function to halt the cell cycle progression within G1 phase

Question 8

Neoplastic tissue = ?

Answer 8

Cancerous tissue

Question 9

Antimetabolites are:

Answer 9

Compounds structurally related to normal cellular compounds

Question 10

Antimetabolites function;

Answer 10

• Inhibit S phase cells
• their mechanism of action involves inhibition of synthesis of PURINE and PYRIMIDINE nucleotide precusors
• They can also fompete with nucleotides in DNA and RNA synthesis

Question 11

Give 2 examples of antimetabolite drug:

Answer 11

• Methotrexate

- 5-fluorouracil

Question 12

Anticancer metabolites

Answer 12

May cause accumulation of G2 phase cells or act without regard to cell cycle phase

Question 13

Give example on anticancer antibiotic

Answer 13

Bleomycin - result in the accumulation of cells in the G2 phase

Question 14

Anticancer antibiotcs function;

Answer 14

Their mechanism of action involves interacting with DNA and disrupting DNA function

Question 15

What agents is often used to treat solid tumors with low growth fractions

Answer 15

Anticancer antibiotics

Question 16

Mitotic spindle poisons

Answer 16

• Disrupt spindle formation and affect cells in mitosis

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Question 17

What if retinoblastoma protein (RB) ?

Answer 17

Tumor supressor protein that functions to halt the cell cycle in resting or G1 phase.
In resting cells, it has less phosphorylated aa residues
In active cycling cells, it is hyper phosphorylated as a result of growth factor stimulation and signaling via MAP kinase.

Question 18

How does RB work in resting cells?

Answer 18

It contains few aa phosphorylated residues, so it prevents entry of cell into S phase by binding to TRANSCRIPTION FACTOR E2F + binding partner DP1/2 .
Note: transcription factor E2F and binding partner DP1/2 are critical for cell to process to the S phase.

Question 19

How does RB work in actively cycling cells?

Answer 19

• RB progressively is hyperphosphorylated as a result of MAP kinase activity as a result of which D-CDK4/6 complexes are activated and they phosphorylate RB.
• further phoshprylation of RB by E-CDK2 allows the cell to move out of G1
• this hyperphosphorylated RB can not inhibit transcription factor E2F and its partner DP1/2 as a result of which they bind to DNA
• binding of E2F to DNA = activated genes whose products are imp for S phase.

Question 20

Examples of EF2 regulated genes ?

Answer 20

Thymidine kinase and DNA polymerase

Question 21

What is p53?

Answer 21

A tumor supressor protein that plays major role in G1. This protein activates and phosphorylates as a result of nuclear DNA damage and produces p21 to halt cell cycle progression.

Question 22

What cyclin dependent kinase inhibitors inhibit Cyclin D?

Answer 22

INK4

Question 23

What are potent inhibitors of CDK2 kinases?

Answer 23

CIP/KIP

note: p21 is a member of CIP/KIP family

Question 24

CDK1 is phosphorylated on?

Answer 24

Tyrosine residues

Question 25

What’s the function of cdc25C?

Answer 25

It catalyzes the removal of inhibitory phosphorylations from CDK1

Question 26

Cdc25C is inactivated by what tumor supressor proteins ?

Answer 26

ATM & ATR

Question 27

Types of DNA damage?

Answer 27

• Replication errors
• chemical exposure
• oxidative insults
• cellular metabolism

Question 28

ATM acts to what kind of DNA damage?

Answer 28

It’s is a primary mediator to the response of double-strand DNA breaks

Question 29

ATR acts on what kind of DNA damage?

Answer 29

It mediates UV-induced DNA damage

Note: also has secondary role in response to double strand DNA breaks

Question 30

What protein plays a role in repair of DNA?

Answer 30

BRCA1

Question 31

Anti cancer antibiotic accumulating in G2 phase?

Answer 31

Bleomycin

Question 32

Drugs inhibiting M phase cells during metaphase?

Answer 32

Mitotic spindle poisons
They dons by binding to tubulin and disrupting the spindle apparatus of microtubules
Eg. Vincristine, vinblastine, taxol