Mitosis/Cell Cycle Regulation

Question 1

What are the the two proteins that control cell division

Answer 1

1. Cyclin dependent kinases: phosphorylates things

2. Cyclins: kinase reg proteins

Question 2

Cell cycle is initiate in response to external signals:

Answer 2

If external factors arent present to stimulate movement into the cell cycle, cells move out of it: G0, they are not replicating. Need Forces that could be hormonal or G1 cyclins

Question 3

____ is an important transcription factor.

Answer 3

Myc: oncogene that act proteins req for cell cycle reg.

Question 4

G1 complex is: ____D. G1S cdk in important in cyclin ____. S-Cdk is important in cyclin ____. M-Cdk is important in cyclin ____

Answer 4

cyclin; E; A; B

Question 5

Growth factors and inflammation upregulate cylin ____

Answer 5

D

Question 6

SCF and APC are:

Answer 6

ubiquitin ligases which cause them to be degraded. Want to get rid of cyclins to get from one portion of cyclin to another.

Question 7

G1S checkpoint is most important check point for cell. The cyclin here is _____:

Answer 7

p53 and rB protein work. Two big suppressor proteins we know of; E

Question 8

How is cdk/cyclin regulated

Answer 8

1. cyclic proteolysis
2. transcriptional regulation (cyclin D)
3. inhibitor proteins (CKI’s)
4. Covalent modification (phosphorylation)

Question 9

Need cyclin ___ in order to enter into G1

Answer 9

D

Question 10

The protein req for ubiquitin ligases are: ____ and APC. The proteins req for TF;s are ___ ___ ___. The tumor supressor proteins are ____ and ____. Proteins req for kinases are ___ and _____. The proteins for phosphatases are _____

Answer 10

SCF; Jun, Fos, Myc, E2F (reg at G1s checkpoint)

p53, pRb; CAK, Wee1; Cdc25

Question 11

p21 is ____inhibitor

Answer 11

CDK (cyto kinase)

Question 12

What needs to happen during cell division

Answer 12

1. must not replicate DNA that has been damaged
2. Must replicate only one complete copy of the genome
3. must properly segregate a complete copy to each daughter cell.

Question 13

What are the 5 critical DNA damage checkpoints

Answer 13

1. G1/S: Dna damage assesment
2. Mid S: DNA replication cp 1
3. G2/M DNA rep cp2
4. M: spindle assembly cp
5. Post M : polyploidy cp (still a single nucleus)

Question 14

what do tumor suppressors do

Answer 14

proteins which serve as cp’s for the cell cycle. monitor for irreparable damage to DNA. Send cells into programmed cell death.

Question 15

what is the guardian of the genome

Answer 15

1. halts cell cycle in response to DNA damage and allows time for repair. Mutation of p53 converts it from a tumor suppressor to an oncogene…mutant p53 is associated with 50% of all tumors

Question 16

Which enzmyes does p53 regulate?

Answer 16

1. p21: mitotic arrest

2. GADD45: DNA repair protein

Question 17

how does p53 work

Answer 17

1, dna damage occuring. p53 gets activated by ATM/ART kinase. STarts transcribing genes one is which p21, which inhibits cdks. pRb is inactivated/phosphortylated in response to cdk2 and inhibts E2F from acting (repressor protein). As long as pRb is not phosphorylated, it binds to E2f and keeps it from going to the nucleus and upregulating all the genes needed for DNA synthesis. If p21 is here pRb stays to E2F (doesnt get phosphorylated) and halts cell cycle completely which is what we want for damaged cells.

Question 18

If progress through G1/S…systems are in place to ensure that replication will initiate once, at each origin of replication during ____phase. Systems are in place to ensure that replication is complete before initiation of ____ phase. ___ phosphorylates APC, an E3 ubiquitin ligase.

Answer 18

S; M; M-cdk

Question 19

m-cdk is cyclin ____ complex

Answer 19

B CDK

Question 20

M-cdk inactivation required in order to move into _____

Answer 20

anaphase

Question 21

M-cdk is required for cells to enter the M phase (mitosis) after G2. What are the phases of mitosis?

Answer 21

1. prophase: chromosomes condense, nucleoli disappear, mitotic spindle forms.
2. prometaphase: nuclear membrane breaks down; chromosomes attach to spindle.
3. metaphase: chromosomes maximally contracted and arrange at equatorial plane
4. anaphase: centromeres split and sister chromatids sep to opp poles.
5. telophase: chromosomes decondense, nuclear membrane reforms, cytokineses

Question 22

what does M-cdk target

Answer 22

1. Condensins: proteins inv in chromosome condensation

2. Laminin: phosphorylation of laminin causes it to depolymerize, resulting in nuclear env breakdown.

Question 23

what are APC effects

Answer 23

1. Securin: separase inhibitor; an APC target..initiates anaphase
2. Separase: a protease that targets cohesin to allow sister chromatid sep
3. Cohesins: hold sister chromatids together.

Question 24

What are APC targets:

Answer 24

cyclin B (which has to disappear in order to enter anaphase)

securin: inhibitor of separase
separase: cleaves cohesin, and allows onset of anaphase

Question 25

when we end mitosis we have No ____

Answer 25

cyclins

Question 26

How needs to happen for programmed cell death

Answer 26

1. removal of factors: loss of mitogenic factors
2. extracellular signals: FasL, TNFalpha, TGFbeta
3. Cell damage: DNA damage, oxidative stress, etc.

Question 27

what are the proteins involved in programmed cell death

Answer 27

1. death domain receptor: Fas
2. tumor suppressors: pRb, p53
3. mitochondrial proteins: cytochrome c, Bcl2
4. caspases: diassembles cytoskeleton and allows act of other enzymes that breakdown DNA
5. endonucleases
6. CKIs

Question 28

____form the pore to release cytochrome c

Answer 28

Bcl2; promotes survival

Question 29

Mutated forms of normal proteins involved in control of cell growth:

Answer 29

oncogenes; some were first identified in tumor causing viruses

Question 30

what are Gain of function type of mutations

Answer 30

being activated without any ligand bonding. GF receptors are being turned on w/o GF binding.

Question 31

Mutant ___ proteins and Tyrosine kinases are known _____

Answer 31

G; oncogenes

Question 32

What are the proteins involved in oncogenic activity

Answer 32

1. erbB: encodes EGF receptor lacking EGF binding domain
2. sis: encodes a G protein with no intrinsic GTPase activity
3. ras: encodes a G protein with no intrinsic GTPase activity
4. myc: encodes a TF that reg’s proliferative proteins.

Question 33

what is HPV

Answer 33

associated with cervical cancer; its common in our machinery intended to reg our cell cycle. HPV early proteins E6 &E7 bind and inactivate p53 and pRb tumor suppressor proteins which causes cell cycle control to be unregulated. BCl2 is also targeted by HPV E6 which helps to maintain cell that should undergo apoptosis.