13.2 Cell Control III

Question 1

The cell cycle can be altered and blocked by what kind of signaling factors?

Answer 1

Altered by mitogens and growth factors (mitogens stimulate the Ras/MAPK signaling pathway.

blocked by things like DNA damage and cell cycle check points

Question 2

What signaling factor stimulates the Ras/MAP kinase pathway? What does the Ras/MAP kinase pathway do?

Answer 2

Mitogen stimulates the Ras/Map Kinase pathway. This pathway activates myc, which activates the cell cycle and regulates gene expression by activating G1-CDK

Question 3

What is myc and what pathway targets this gene?

Answer 3

myc is a gene that was discovered b/c it causes myelocytomatosis, which is a cancer caused by uncontrolled growth of lymphocytes aka lymphoma. Myc activates cell cycle

myc is one of the major targets for the MAP kinase pathway

Question 4

what does myc regulate?

Answer 4

My regulates cell cycle activity
Myc also regulates gene expression and one of the gene that myc controls is a gene coding for expression of a G1 specific cyclin which activates G1-Cdk

Question 5

What is the role of G1-CDK in cell division?

Answer 5

G1-Cdk alters the activity of a protein called Rb, which inactivates transcription factor E2F. G1/Cdk alters Rb by phosphorylating it and phosphorylated Rb releases the E2F protein

Question 6

How were RB (retinoblastoma) proteins first identified?

Answer 6

b/c mutations in them alter their functitastomas. Rb stands for retinoblastoma

Question 7

What is the function of Rb (retinoblastoma) proteins?

Answer 7

The function of Rb proteins is to inactivate transcription factor E2F

Question 8

What is the function of E2F? What inactivates E2F

Answer 8

E2f is a transcription factor that controls the expression of many proteins that are needed to enter the cell cycle at G1, including G1/S cyclin and S cyclin and E2F itself, making a positive feedback loop.

Rb (retinoblastoma) protein inactivates transcription factor E2F

Question 9

What creates an increase of expression in G1/S and S phase cycling genes?

Answer 9

increase in expression of G1/S and S phase cyclin genes is enhanced by positive feedback loops.

Question 10

What inactivates the Rb (retinoblastoma) proteins?

Answer 10

G1/S-Cdk and S-Cdk can phosphorylate Rb making them inactive

Question 11

What is p53?

Answer 11

protein P53 controls/regulates cell cycle checkpoints.

Question 12

Under normal conditions, the protein p53 is inactivated by two different mechanisms. What are those two mechanisms?

Answer 12

1) p53 is not stimulated so it’s expression is low
2) cells have a mechanism for targeting any small amount of p53 that’s around for degradation using the proteasome system. This targeting mechanism requires a protein called Mdm2, which recruits ubiquitin ligase to p53

Question 13

How do cells upregulate (activate it) the amount of p53?

Answer 13

ATM/ATR can phosphorylate p53 which releases it from its inhibitor Mdm2.

Question 14

How does p53 shut off cell cycle progression?

Answer 14

Two ways

1) first is if there is DNA damage, the cell will use the ATM/ATR kinases. DNA damage activates ATM/ATR kinases which signals checkpoint 1 and 2. This leads to phosphorylation of p53. When phosphorylated, Mdm2 will release p53, making p53 active. p53 expresses p21cdk inhibitor genes and this blocks signaling of G1/S CDK and S CDK. So the cell will not enter S phase
2) Myc can also regulate p53. If there is excessive Myc production, then Myc will recruit Arf. Arf can inactivate Mdm 2, causing Mdm2 to release p53. Again p53 can arrest the cell cycle or lead to apoptosis.

Question 15

What is one important system that use p53 to block the progression fo cells through the cell cycle?

Answer 15

one of the most important is the system that prevents cell cycle progression if DNA has been damaged. Cells, like skin cells, end up having DNA damage occur many times every day and if these cells were allowed to divide w/o fixing their DNA, we would have problems with many types of cancer.

Damage to DNA activates two kinases (1. ATM and ATR)

Question 16

What does Mdm2 do?

Answer 16

It inhibits p53

Question 17

Excessive Myc signaling can lead to?

Answer 17

activation of p53

Question 18

What happens when people have mutations in ATM, ATR?

Answer 18

people w/mutations in these genes are prone to developing cancer and rarely live longer than their mid-20s.

Question 19

What happens when there’s a breakage of DNA? What detects this breakage and what does it lead to?

Answer 19

Breakage of DNA is detected by a complex series of proteins that leads to the activation of ATM/ATR kinases.Which ultimately phosphorylate p53 and activate it’s activity for cell arrest (cell won’t enter S phase)

Question 20

What is one of the downstream genes that is expresses when p53 is activated?

Answer 20

p21 Cdk inhibitor and this inhibitor acts to prevent signaling by G1/S and S phase cyclin dependent kinases so that effectively prevents the cell from entering S phase.

Question 21

How can cells detect when growth factor signaling is abnormally long?

Answer 21

Prolong activity of Myc leads to the activation of a protein called Arf, which affects the p53 signaling pathway and leads to cell cycle arrest and cell death

Question 22

Why is cancer thought to require more than one defect in cell cycle regulation in order to proceed?

Answer 22

B/c there are multiple pathways that prevent uncontrolled cell division such as Myc and Arf, ATM/ATR, and Mdm2.

Question 23

How do cells control cell growth?

Answer 23

through Pi 3-kinase signaling system and its ability to activate Akt. Activation of this pathways also activates TOR or mTOR, which regulates growth.

Question 24

How does TOR/mTOR regulate/increase cell growth?

Answer 24

1) TOR activates two gene regulatory kinases S6 Kinase and 4E-BP. S6 kinase activates S6 protein and 4E-BP activates eIF43 protein
2) These proteins are involved in the production and function of ribosomes which are needed in order for cells to make proteins and to grow.

AKA mTOR facilitates the function of ribosomes and the production of protein

Question 25

What does mTOR facilitate?

Answer 25

the function of ribosomes and the production of proteins

Question 26

What do MADs regulate?

Answer 26

the metaphase to anaphase transition checkpoint.

Question 27

What can happen if chromosomes don’t attach to the mitotic spindle correctly?

Answer 27

they will have a high probability of being distributed into the two daughter cells in an uncontrolled manner and even if one chromosome doesn’t segregate correctly this can bring about cell death or generate cells that become cancerous and grow uncontrollably

Question 28

What does MAD2 stand for and what is its role?

Answer 28

“Mitotic Arrest Deficient.”

The recruitment of MAD2 activates the MAD2 protein, which inhibits the function of the protein CDC20. AKA cell can’t go into anaphase. In the presence of activated MAD2, cells are going to remain in metaphase, long enough to allow the lost chromosomes time to attach to the mitotic spindle

Reminder: CDC20 is involved in the activation of the anaphase promoting complex, which triggers the metaphase/anaphase transition.

Question 29

Cells that lack MAD are defective in what way?

Answer 29

in their ability to halt mitosis