Growth And Division Of Cell

Question 1

3 roles of Mitogenic and growth factors

Answer 1

1. Stimulate cell division (eg. Hormones (Oestrogen), cytokines/growth factors(EGF))
2. Stimulate protein synthesis (eg. mTOR pathway)
3. Survival factors prevent apoptosis (maintain the balance between cell death and cell division)

Question 2

What are the regulatory progress involved in cell growth and cell cycle regulation?

Answer 2

1. Cell cycle progression
2. Cell cycle checkpoints
3. Role of tumour suppressors
4. cdc25c phosphate-CDK 1 regulation

Question 3

What are the regulators of cell cycle progression?

Answer 3

[Cyclins, Cyclin-dependent kinases (CDKs)]—> forms Cyclin-CDKs Complex

Cyclin-dependent kinase inhibitors (CDKi)

Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells.

Question 4

What are the extracellular factors that regulate cell growth and proliferation?

Answer 4

1. Mitogenic
2. Growth factors (EGF, BFGF, BDGF)
3. Extracellular matrix (cell-cell/ cell-matrix contact)
4. Ions such as Ca2+

Question 5

What are the cyclin and kinase involved in

Function: Progression past the restriction point at the G1/S boundary

Answer 5

Cyclin: D
Kinase: CDK4, CDK6

Question 6

What are the cyclin and kinase involved in

Function: Inhibition of DNA synthesis in early S phase

Answer 6

Cyclin: E,A
Kinase: CDK2

Question 7

What are the cyclin and kinase involved in

Function: Transition from G2 to M

Answer 7

Cyclin: B
Kinase: CDK1

Question 8

What are the 3 checkpoints that are being regulated at cell cycle?

Answer 8

G1 (Restriction) Checkpoint
G2/M checkpoint
M (spindle/ metaphase-anaphase) checkpoint

Question 9

What is checked during

G1( Restriction checkpoint)

Answer 9

Integrity of DNA and other external factors

Influenced by
Growth factors
Nutrients
Cell size
DNA damage

Question 10

What is checked during

G2 (G2/M) checkpoint

Answer 10

Completely replicated chromosome and DNA damage

Influenced by
Cell size
DNA damage
DNA replication

Question 11

What is checked during

M (spindle/ Metaphase-Anaphase) checkpoint

Answer 11

Ensure all sister chromatids are correctly attached to the spindle microtubules before cell enters the irreversible anaphase stage

Influenced by
Chromosome attachments to spindle

Question 12

What protein is involved in checkpoint regulation?

Answer 12

Retinoblastoma Protein (RB protein)
-Tumour suppressor function in resting or G1 phase of the cell cycle

Question 13

How does RB protein regulate cell cycle in

Resting cells

Answer 13

Partially phosphorylated Retinoblastoma (RB) protein, which prevents entry into S-phase by binding to transcription factor E2F & its binding partner DP1/2 (critical for G1/S transition)

Question 14

How does RB protein regulate cell cycle in

Actively cycling cell

Answer 14

Progressive hyperphosphorylation of Retinoblastoma (RB) protein, which is achieved by
I)Growth factor signaling
II) Activation of Cyclin D-CDK4/6
III) Cyclin E-CDK2

CDK4/6 can be inhibited by p16 (CDKi)

Question 15

If RB protein is hyperphosphorylated during G1 phase, what will happen?

Answer 15

Hyperphosphorylated RB protein will dissociates from E2F and cell moves out of G1

Question 16

What happens if p53 gene is mutated?

Answer 16

Inappropriate cell survival and proliferation

Question 17

What are the factors that stimulate stable, active p53?

Answer 17

1. Hyperproliferative signals
2. DNA damage
3. Telomere shortening
4. Hypoxia

Question 18

What happens when stable active p53 is stimulated?

Answer 18

1. Cell cycle arrest
2. Senescence
3. Apoptosis

Question 19

What are the steps for activation of cell cycle (G2 checkpoint) starting from

Inactive CDK1

Answer 19

Inactive CDK1 –> Cdc25c remove inhibitory P from CDK1 –> CDK1 binds to cyclin B (forms CDK1- cyclin B complex) –>Activate mitosis related subcellular components

Question 20

During G2 checkpoint in cell cycle, what will happen if the cell cycle have to be suspended prior to chromosome segregation?

Answer 20

Cdc25c will be inactivated by ATM and ATR

Question 21

What are the types of DNA damage?

Answer 21

Replication errors
Chemical exposure
Oxidative stress
Production of reactive oxygen species (ROS) during cellular metabolism

Question 22

What are the DNA damage-induced responses?

Answer 22

ATM and ATR, which activates p53

ATM - mediator of the response to dsDNA breaks (by inonization
radiation)

ATR - mediating UV-induced DNA damage

Question 23

What are the response by S phase cell if there is DNA damage?

Answer 23

Rate of DNA synthesis is slower