Cell Cycle, Cancer, Cell Death

Question 1

G1 cyclins include

Answer 1

C, D1

Question 2

S cyclins include

Answer 2

Cyclin A

Question 3

G2/M cyclins include

Answer 3

B 1-2

Question 4

Cyclin H

Answer 4

Constitutive expression

Question 5

Cdk4/Cdk6

Answer 5

Binds with cyclin D
Phosphorylation of retinoblastoma susceptibility protein (pRb) in G1
Triggers passage of the restriction point, and cyclin E synthesis in some cells

Question 6

Cdk2

Answer 6

Binds with cyclin E and A

Triggers G1–>S transition

Question 7

Cdk1

Answer 7

Binds with Cyclin B, triggers G2–>M transition

Question 8

Cdk activation

Answer 8

Cdks have 3 phosphate binding sites. Phosphorylation of one of these sites activates it, while phosphorylation of the other 2 sites inactivates it.
The complex must be phosphorylated on the first site, and dephosphorylated (by protein phosphatase cdc25) on the other two sites to be active

Question 9

Cdc25A phosphatase

Answer 9

Acts on Cdk1, Cdk2

Promotes G1–>S and G2–>M transitions

Question 10

Cdc25B phosphatase

Answer 10

Acts on Cdk1

Promotes G2–>M transition

Question 11

Cdc25C phosphatase

Answer 11

Acts on Cdk1
Promotes G2–>M transition
Dephosphorylates Cdk1 complexed to cyclins A/B

Question 12

CKI: p21

Answer 12

Induced by p53 tumor suppressor. Cell cycle arrest after DNA damage. Binds most Cdk-cyclin complexes

Question 13

CKI: p27

Answer 13

Cell cycle arrest in response to growth suppressors like TGF-b
Binds Most Cdk cyclin complexes

Question 14

INK4: p16

Answer 14

Cooperates with retinoblastoma susceptibility protein pRb in growth regulation. Cell cycle arrest in senescence.

Question 15

What are the common substrates for all INK4 cyclin inhibitors

Answer 15

Cdk4 and Cdk6

Question 16

What is the predominant cyclin during G1 phase

Answer 16

Nuclear D1

Question 17

Explain cyclin/Cdk activity during the G1/S transition

Answer 17

E-CDK2 complexes hyperphosphorylate pRb, which liberates E2F transcription factors from pRb control, enabling E2Fs to trigger increased transcription of the cyclin E and E2F1 genes. This leads to synthesis of more cyclin E and formation of more E-CDK2 complexes, which then amplify the process by hyperphosphorylating more pRb. E2F1 amplifies its own activity

Question 18

G2/M transition cyclin/CDK activity

Answer 18

Activation of CDK1/Cyclin B at the G2/M boundary by Cdc25 phosphatase. CDK1/Cyclin B translocate to nucleus and initiate spindle assembly. Activated anaphase promoting complex APC destroy CDK1, freeing cyclin B for degradation

Question 19

What happens if DNA damage is detected during G1 checkpoint (fast and slow pathways)

Answer 19

Slow pathway involves stabilization of p53 and upregulation of p21 which inhibits cyclin/Cdk complexes
Fast pathway activates Chk2 and inactivates Cdc25 so that inhibitory phosphates of Cyclin E/Cdk2 complexes are not removed

Question 20

p16 function during G1 checkpoint damage

Answer 20

p16 prevents pRb phosphorylation via inhibition of Cdk4/Cdk6 kinases

Question 21

What protein is responsible for activating the inhibitory proteins such as p53 and Chk2

Answer 21

ATM

Question 22

Is the initiation step of carcinogenesis reversible

Answer 22

No

Question 23

Is the promotion step of carcinogenesis reversible

Answer 23

Only in its early stages

Question 24

Initiation vs promotion

Answer 24

Initiation is the original even that causes a change in cellular DNA sequence
Promotion involves gene activation or repression such that the latent phenotype of the initiated cell becomes expressed through cellular selection and clonal expansion

Question 25

Progression of carcinogenesis

Answer 25

Involves further complex irreversible genetic changes such as translocations, deletions, gene amplifications. Results in the conversion of benign tumors into malignant neoplasms

Question 26

Retrovirus type 1- transducing viruses

Answer 26

Cellular oncogene is carried in retrovirus

Question 27

Retrovirus type 2- non transducing viruses

Answer 27

Cellular oncogene activated by proviral insertion/integration

Question 28

Retrovirus type 3 non transducing long latency viruses

Answer 28

Retroviral transactivating protein disrupting normal regulation of cellular transcription

Question 29

Retrovirus type 4- retroviruses that contain an envelope that signals

Answer 29

Inappropriate cellular signaling resulting from viral envelope/cell receptor interaction (acts like mitogen)

Question 30

Tumor suppressor genes are all what type of proteins

Answer 30

Cell cycle regulatory proteins such as p53, Rb, p16

Question 31

Radiation is most effective on cells which have

Answer 31

Reproductive activity | Longer dividing future ahead

Question 32

Alkylating agents

Answer 32

Denature DNA macromolecules

Question 33

Intercalating agents

Answer 33

Intercalate b/w two bases, inducing structural/functional changes- capable of breaking DNA molecuels

Question 34

Antimetabolites

Answer 34

Structural analogs of purines/pyrimidines- block the synthesis of corresponding bases

Question 35

Mitostatic agents

Answer 35

Inhibit tubulin synthesis- cell spindle poisons

Question 36

Platinum derivatives

Answer 36

Bind DNA

Question 37

Main proteins involved in necrosis

Answer 37

Receptor-interacting protein 1 RIP1 | Poly (ADP-ribose) polymerase 1 PARP-1

Question 38

Necrosis mechanism

Answer 38

``` Ca2+ overload Mitochondrial uncoupling Increased O2 consumption and excess ROS production ATP depletion No caspases involved ```

Question 39

Does apoptosis cause inflammation

Answer 39

No, necrosis does

Question 40

Apoptosis mechanisms

Answer 40

ATM/p53 activation by DNA damage Death receptors- Fas, TNF- Caspase 8 mediated Sphyngomyelinase activation-->ceramide formed Mitochondrial damage mediated by ceramide

Question 41

Bax/Bak, BH3 only function

Answer 41

Bax/Bak induce permeabilization by forming pores BH3-only family members activate Bax/Bak by binding/inhibiting anti-apoptotic Bcl-2 proteins and directly bind Bax/Bak and activate them (apoptosis)

Question 42

Major differences b/w autophagy and apoptosis

Answer 42

No nuclear or DNA fragmentation

Question 43

Autophagy quick overview

Answer 43

Release of beclin from Bcl-2, which can then form the PI3K that contributes to formation of nucleation complex. Two independent conjugation cascades mediated by LC3-II and Atg5-12 Transmembrane Atg9 delivers additional membranes

Question 44

Mitotic catastrophe

Answer 44

Caused by aberrant mitosis Mainly associated with deficiencies in cell cycle checkpoints -Involves formation of giant cell with large cytoplasm, no change in membrane Formation of nuclear envelopes around clusters of mis-segregated chromosomes Abnormal Cdk1/Cyclin B activation