High Yield Cell Cycle/Cancer

Question 1

Which cyclin-CDK complex triggers the G2 to M transition?

Answer 1

Cyclins A or B and Cdk 1 (mostly B though)

Cyclin A is synthesized in S and destroyed at prometaphase; Cyclin B is synthesized in S/G2 and destroyed following the completion of chromosome attachment to the spindle

Question 2

Which cyclin-CDK complex triggers the G1 to S transition?

Answer 2

Cyclins A and E and Cdk 2

Question 3

Which cyclin-CDK complex triggers the passage of the restriction point and cyclin E synthesis and leads to the phosphorylation of the retinoblastoma susceptibility protein in G1?

Answer 3

Cyclin D and Cdk’s 4/6

Extracellular growth factors control the synthesis of D cyclins

Question 4

Which CKI’s (cyclin-dependent kinase inhibitors) inhibit the cyclin D-Cdk 4/6 complex?

Answer 4

p15 (INK4B), p16 (INK4A), p18 (INK4C), p19 (INK4D)

Question 5

Which CKI’s (cyclin-dependent kinase inhibitors) inhibit the cyclin E-Cdk 2, cyclin A-Cdk 2, and cyclin B-Cdk 1 complexes?

Answer 5

p21 (Cip1), p27 (Kip1), p57 (Kip2)

Question 6

What is the function of p21 (Cip1)?

Answer 6

Cell cycle arrest after DNA damage; induced by p53 tumor suppressor

Question 7

What is the function of p27 (Kip1)?

Answer 7

Cell cycle arrest in response to growth suppressors like TGF-beta and in contact inhibition and differentiation

Question 8

What is the function of p16 (INK4A)?

Answer 8

Cooperates with the retinoblastoma susceptibility protein in growth regulation; cell cycle arrest in senescence; altered in high % of human cancers

Question 9

What is the slow pathway of the G1 checkpoint?

Answer 9

Stabilization of p53 and transcriptional upregulation of p21 which binds and inhibits the cyclin-CDK complexes

Question 10

What is the fast pathway of the G1 checkpoint?

Answer 10

Activation of Chk2 and the inactivation of Cdc25, thus inhibitory phosphates of the cyclin E-Cdk2 complex can no longer be removed

Question 11

What is the ARP/p16 pathway of the G1 checkpoint?

Answer 11

Downstream signaling, G1 arrest via p53 and p21 transcription, or directly CDKI p16 will prevent Rb phosphorylation via inhibition of the Cdk 4 and 6 kinases; these cells almost never enter mitosis

Question 12

What is the G2 checkpoint?

Answer 12

After DNA damage, Chk1/2 target Cdc25 for nuclear export leading to the accumulation of the inactive cyclin B-Cdk 1 complex; further inhibition of this complex takes place through a slower p53 dependent pathway; the lack of activated complex interrupts the feedback loops resulting in G2 arrest

Question 13

What is a neoplasm?

Answer 13

Relatively autonomous abnormal growth with abnormal gene regulation; 2 types (benign or malignant)

Question 14

What is a tumor?

Answer 14

Space occupying lesions that may or may not be neoplasms

Question 15

What is cancer?

Answer 15

Malignant neoplasm

Question 16

What is metastasis?

Answer 16

Secondary growth of cancer at different location from primary neoplasm

Question 17

What are the stages of carcinogenesis?

Answer 17

Initiation (genotoxic event): simple mutation in one or more genes that control key regulatory pathways of the cell; irreversible
Promotion (epigenetic event): selective functional enhancement of signal transduction pathways that were induced by initiator by continuous exposure; reversible
Progression (clastogenic event): continuing change of the basically unstable karyotype

Question 18

What is the mechanism and oncogenic element of transducing viruses?

Answer 18

Mechanism: oncogenic transduction of cellular gene

Oncogenic Element: cellular oncogene carried in retrovirus

Question 19

What is the mechanism and oncogenic element of non-transducing viruses?

Answer 19

Mechanism: cis-acting provirus

Oncogenic Element: cellular oncogene activated by proviral insertion/integration

Question 20

What is the mechanism and oncogenic element of non-transducing long latency viruses?

Answer 20

Mechanism: trans-acting proteins encoded by retrovirus

Oncogenic Element: retroviral transactivating protein disrupting normal regulation of cellular transcription

Question 21

What is the mechanism and oncogenic element of retroviruses that contain an envelope that signals?

Answer 21

Mechanism: trans-acting protein (envelope) encoded by retrovirus

Oncogenic Element: inappropriate cellular signaling resulting from viral envelope/cell receptor interactions

Question 22

What are some different viral oncogenes?

Answer 22

Adenovirus, hepadnavirus, herpesvirus, flavivirus, papillomaviruses, polyomavirus, and retroviruses

Question 23

What are some oncogenes?

Answer 23

Ras, Myc, Cyclin D, Cyclin E

Question 24

What are some tumor suppressor genes?

Answer 24

P53, Rb, p14ARF, p16 (INK4A)

Question 25

When is radiation most effective for treating cancer?

Answer 25

Cells have reproductive activity, longer dividing future ahead, and with morphology and function least fixed

Question 26

What is the mechanism of necrosis?

Answer 26

Ca2+ overload leads to mitochondrial uncoupling of OxPhos, which leads to increased O2 consumption and excessive ROS production, and this leads to ATP depletion; mediated by RIP1 and PARP-1

Question 27

What are the triggers for apoptosis?

Answer 27

DNA damage, death receptor signaling, cell membranes, and mitochondrial damage

Question 28

What are the mechanisms for the induction of the mitotic catastrophe?

Answer 28

Defects in cell cycle checkpoints, hyperamplification of centrosomes, and caspase-2 activation during metaphase (which delays apoptosis); cells will either die without exiting mitosis, continue dividing and then die, or undergo permanent G1 arrest