Cancer - Cell Cycle

Front 1

Match the following: A)Hepatocytes, cardiac muscle cells, digestive epithelial cells, neurons… B) G0 (quiescent cells), permanent cells, daughter cells (enter cell cycle)

Back 1

1. G0 (quiescent cells): hepatocytes (go in-&-out of the cell cycle)… 2. Permanent cells (don't re-enter the cell cycle): neurons/cardiac muscle cells… 3. Daughter cells (enter the cell cycle): digestive epithelial cells

Front 2

At which cell cycle stage is p53 most active?

Back 2

G1 check point before entering the S-phase

Hint 2

None

Front 3

What effect does Cdk have on the Rb protein? And which would be an oncogene and which would be a tumor suppressor?

Back 3

Cdk phosphorylates the Rb protein (where the Rb protein has been sequestering the transcription factor E2F)… 2) Cdk is an oncogene AND the Rb gene would be a tumor suppressor

Hint 3

None

Front 4

Describe Cdk's suppression of the Rb protein mechanism.

Back 4

Mitogen activate cyclin --> leads to cyclin binding to the G1/S-Cdk (kinase) --> The G1/S-Cdk is phosphorylated by two kinases (CAK-activating and Wee1-inactivating) --> Cdc25 phosphatase removes the inactivating phosphate) --> active G1/S-Cdk can then phosphorylate the Rb protein (causing it to release EF2)

Front 5

In the M-Cdk activation pathway, where is the site of positive feedback?

Back 5

Active G1/S-Cdk activate the Cdc25 phosphatase, which leads to the dephosphorylation of the inactive G1/S-Cdk

Front 6

What type of cancer is the Rb protein (tumor suppressor) associated with?

Back 6

Retinoblastoma (childhood eye-tumor)

Front 7

What associates with the active Rb-E2F complex? What is its effect?

Back 7

HDAC… HDAC makes the histones more compact and less accessible to transcription factors

Front 8

What causes the release of HDAC?

Back 8

G1/S-Cdk

Front 9

1. What is APC's role?... 2. what activates it?… 3. What cancer is the truncation of APC associated with?

Back 9

APC (anaphase promoting-complex) is a ubiquitin ligase, which ligases the ubiquitin to the Cdk and leads to the degradation of activated the cyclin… 2. Cdc20… 3. FAP

Front 10

1. Describe the mechanism that controls activated Cdk by degradation... 2. Describe the mechanism that controls activated Cdk by sequestration

Back 10

1. Active APC, Cdc-20 (APC activating subunit, ubiquitin and ubiquitin enzymes (E1 and E2) --> leading the degradation by proteosomes... 2. DNA damage --> release of Mdm2 from p53 and p53 is phosphorylated(transcription factor)--> p53 transcribes p21 --> p21 protein inhibits Cdk-cyclin activity

Hint 10

None

Front 11

1. What is inactive p53 bound to that inhibits its activity?… 2. What activates p53?

Back 11

1. Mdm2… 2. X-rays (other DNA damage)

Front 12

1. What is the role of p21?… 2. Describe the mechanism of p21.

Back 12

Prevents gene transcription by binding activated Cdk… 2. X-rays damage DNA --> Mdm2 is released from p53 as p53 is phosphylated --> p53 is a transcription factor for p21 --> p21 is transcribed --> translated p21 --> p21 binds Cdk and inhibits its activity

Hint 12

None

Front 13

What is CPT-11 (Irinotecan)?

Back 13

a DNA damaging agent (drug)

Front 14

What is the effect of CPT-11?

Back 14

DNA damage --> p53 induction --> p21 expression --> cell arrest

Front 15

What is added to CPT-11 to cause apoptosis?

Back 15

Flavopiridol (Flavopiridol + CPT-11 --> apoptosis)

Front 16

What effect will a p53 mutation have on the use of CPT-11 + flavopiridol?

Back 16

mutations make this chemotherapeutic combination less effective