Cell Cycle

Question 1

Pair the Cyclins with there kinases and function (Positive Regulators)
A
B1 and B2
D1-D3

Answer 1

Cdk1- triggers G2-M
for both A and Bs

Cdk4 and 6- phosphorylates protein pRB (retinoblastoma-a tumor suppressor) in G1

Question 2

What substrates to Enzymes Cdc25A, B, and C bind

and what phases do they promote? (Positive Regulation)

Answer 2

Cdk1 for all
G1-S and G2-M
G2-M
G2-M also dephos Cdk1

Question 3

Pair the main Negative Regulators with substrate and function
p21
p27
p16

Answer 3

Most cdk-cyclin complexes- induced by p53 tumor suppressor. Promotes cell cycle arrest and can help assemble active cdk complexes
Most cdk-cyclin complexes- Cell cycle arrest in response to growth suppressors like TGF-beta
Cdk4, Cdk6- Communicates with retinoblastoma protein prB in Growth regulation; altered in many human cancers**

Question 4

What controls the restriction point in G1 phase?

Answer 4

phosphorylation of retinoblastoma (pRb) causes its release which then causes E2F to hyperphosphorylate–the cell is committed

Question 5

What does E2F do?

Answer 5

Controls DNA synthesis and cell cycle/ involved in R point of G1

Question 6

What must be removed from CdK1 in G2 to activate it, driving cell to M phase?

Answer 6

Threoinine by CAK
and
Phosphate by CDC25

Question 7

Difference between Tumor, Neoplasm, Cancer, Metastasis

Answer 7

Tumors – Space occupying lesions that may or may not be neoplasms
Neoplasms – Autonomous abnormal growth with abnormal gene regulation
Cancer – Malignant neoplasm (metastasis can occur)
Metastasis – Secondary growth of cancer at another location

Question 8

What are the hallmarks of Cancer

Answer 8

I'm a Gimp Rag
Immune Destruction
Metastasis
Angiogenesis (new blood ves)
Genome instability
Infammation
Reprogram E metabolism
Acquire Self Sufficiency
Growth Inhibitory ignored

Question 9

What are RAS proteins?

Answer 9

Transmit signals for cell division in humans

-Oncogenes.. overexpression can lead to cancer

Question 10

Classes of Oncogenic Retroviruses

What is the mechanism and Onogenic Element for Type 4: Retrovirus with an envelope

Answer 10

Transacting protein envelope encoded by retroviruses

Inappropriate cell signaling due to envelope/cell receptor interactions

Question 11

Classes of Oncogenic Retroviruses

What is the mechanism and Onogenic Element for Type 1: Transducing Viruses

Answer 11

Oncogenic transduction of cellular gene

Cellular oncogene carried in retrovirus inserted

Question 12

Classes of Oncogenic Retroviruses

What is the mechanism and Onogenic Element for Type 2: Non-transducing viruses

Answer 12

Cis-acting provirus

Cellular oncogene activated by proviral insertion/ integration with genome

Question 13

Classes of Oncogenic Retroviruses

What is the mechanism and Onogenic Element for Type 3: Long latency non-transducing viruses

Answer 13

Trans-acting proteins encoded by retroviruses

Retroviral transactivating protein disrupting normal regulation

Question 14

What can cause a Hepatocellular carcinoma?

Answer 14

Hepadnavirus

Question 15

What does Herpesvirus cause?

Answer 15

Burketts lymphoma, Nospharyngeal carcinoma
hodgkin’s lymphoma
Gastic carcinoma
Castleman’s disease

one type is Epstein-barr virus (EBV)

Question 16

What is Flavivirus?

Answer 16

Hep C– can cause Hepatocellular carcinoma

Question 17

What can Papillomavirus cause?

Answer 17

Anogenital cancer, upper airway cancers
HPV
Skin cancers

Question 18

What are the 3 main tumor suppressor genes and what do they do?

Answer 18

P53

• Controls cell cycle checkpoiont G1 G2,
• Lose control of checkpoint = cancer
• Very prevalent

P16INK4A (P16)

• Stops cell cycle, cells become irreversibly arrested
• Loss of control = unrestricted G1 checkpoint.
• Caused by Gene mutation, deletion, and CpG** island methylation

Rb (Retinoblastoma)
- Effects restriction point (RP), Not limited to loss of both alleles
- Gene may be inactivated, methylated, or sequestered
- Viral gene can cause sequestration
can cause cervical cancer if bound to HPV E7

Question 19

In Chemotherapy, what is the purpose of 
Alkylating agents
Intercalating agents
Antimetabolites (ex. METHOTREXATE)
Mitostatic agents
Platinum Derivatives

Answer 19

• Alkylating agents – denature DNA and macromolecules
• Intercalating agents – intercalate between two bases, causing structure change and possibly breaking DNA bonds (CROSS LINK DNA)
• Antimetabolites (E.g. Methotrexate) – affect pool of purine/ pyrimidines to decrease DNA synthesis
• Mitostatic Agents – inhibit tubulins
• Platinum Derivatives – binds to DNA

Question 20

What are the two players involved in targeting mito in Necrosis, and what are it’s mechanisms?

Answer 20

(i) Receptor-Interacting protein 1 (RIP1)
(ii) Poly [ADP-ribose] polymerase 1 (PARP-1)
1. Causes Ca2+ overload, uncoupled mitochondria, increase O2 consumption, ROS creation by activation of NADPH Oxidase

Question 21

Apoptosis cells, mediators, and effectors

Answer 21

Liquid cells- hematopoietic (stem) cells and malignant counterparts
p53 mediator
Caspases 8*, 9, and 10 initiate
while 3**, 6, and 7 execute

Question 22

In apoptosis, what do Bax and Bak do and what can inhibit their binding?

Answer 22

induce permeabilization by forming pores

BH3

Question 23

What is Autophagy?

Answer 23

Self eating/recycling of a cell

(e) Biochemical Features: Caspase-independent and increased lysosomal activity
(f) Mechanisms:
(i) Autophagy related genes
(ii) Beclin-1 and LC3 which are suppressors
1. Beclin-1 sews a vesicle around the organelle it wants to “eat”
2. This then combines with a lysosome to release food for cell while elongating the nucleation complex
3. This can get out of hand which leads to total cell autophagy

Question 24

Info on Mitotic Catastrophe (

Answer 24

• Mitotic catastrophe (lecture slides) (One of the main mech of cell death in cancer therapies!)
(a) Definition: Aberrant mitosis (stuck dividing) causing cell death, associated with cell cycle checkpoint deficiency
(b) Morphology: No change in membrane, larger cytoplasm w/ GIANT cell (cells can’t divide)
(c) Cells involved: Most dividing cells
(d) Inflammation: No
(e) Biochemical Features: Caspase independent, abnormal CDK1/Cyclin B activation
(f) Mechanisms:
(i) Defects in Cell Cycle Checkpoints
1. P53 – G2 checkpoint
2. BUB-related kinase (BUBR) – spindle checkpoint
3. Increased expression of multiple mitotic checkpoint genes (APC) spindle assembly -
(g) Hyperamplification of centrosomes – usually in subsequent cell cycle –
(h) Caspace-2activation during metaphase – delayed apoptosis
Fate of cells with Mitotic Catastrophe
1) Mitotic Death – Die without exiting mitosis
2) Delayed cell death - Proceed to G1, continue for many cycles (can be years) then die
3) Exit mitosis and undergo G1 arrest (Senescence)

Question 25

What is senescence?

Answer 25

(a) Definition: Permanent cell arrest (reproductive death)
(b) Morphology: No change in membrane, flattening and increased granularity, distinct heterochromatic structure, looks like fried egg
(c) Cells involved: All cells
(d) Inflammation: Yes, but induced by cell itself, can induce inflammatory factors that also effects other cells (e.g. aging)
(e) Biochemical Features:
(f) Mechanisms: Two pathways via P53-P21** or P16-Rb***