BI203 Lecture 23: The Cell Cycle - Regulation of Cdk's (Slides 20 - 35)

Question 1

Proliferation of animal cells is also regulated by extracellular ___ ___ that control progression through the restriction point in late G1.

Answer 1

growth factors

Question 2

Proliferation of animal cells is also regulated by extracellular growth factors that control progression through the restriction point in late ___.

Answer 2

G1

Question 3

Presence of growth factors at the end of G1 leads to synthesis of ___ ___ via the Ras/Raf/MEK/ERK pathway.

Answer 3

cyclin D

Question 4

Presence of growth factors at the end of G1 leads to synthesis of cyclin D via the ___/___/___/___ pathway.

Answer 4

Ras/Raf/MEK/ERK pathway

Question 5

Cyclin D pairs with ___ to form the ___/___ ___ complex to push the cell through the restriction point at the end of G1.

Answer 5

Cdk4,6 Cdk4,6/cyclin D

Question 6

Reminder: ___ ___ ___ can encode transcription factors and activate genes that promote cell proliferation, i.e. cyclin D.

Answer 6

immediate early genes

Question 7

Cdk4,6/cyclin D then induces ___ ___ expression via the transcription factor E2F.

Answer 7

cyclin E

Question 8

Cdk4,6/cyclin D then induces cyclin E expression via the transcription factor ___.

Answer 8

E2F

Question 9

E2F-mediated transcription is inhibited by ___. ___ is phosphorylated by Cdk4,6/cyclin D. ___ releases E2F, activating it.

Answer 9

Rb, Rb, Rb

Question 10

___/___ ___ induces entry into S phase.

Answer 10

Cdk2/cyclin E

Question 11

Rb is a type of ___ ___ ___, a gene whose inactivation leads to tumor development.

Answer 11

tumor suppressor gene

Question 12

___ ___ and the ___ ___ ___ (ORC) bind to replication origins during G1.

Answer 12

MCM helicase, origin recognition complex (ORC)

Question 13

___/___ ___ activates the origin recognition complex (ORC) by phosphorylating activating proteins.

Answer 13

Cdk2/cyclin E

Question 14

Cell cycle arrest occurs due to ___ of Cdk1 and Cdk2.

Answer 14

inhibition

Question 15

___ and ___ are inhibitory kinases of Cdk1 and Cdk2.

Answer 15

Thr-14, Tyr-15

Question 16

___ family = A family of phosphatases that REMOVE inhibitory phosphorylation by Thr-14 and Tyr-15.

Answer 16

Cdc25 family

Question 17

DNA damage checkpoints are mediated by protein kinases ___ and ___.

Answer 17

ATM, ATR

Question 18

ATM and ATR then phosphorylate and activate the checkpoint kinases ___ and ___.

Answer 18

Chk1, Chk2

Question 19

Chk1 and Chk2 then inhibit ___, which leads to phosphorylation of Cdk’s, and arrest of the cell cycle.

Answer 19

Cdc25

Question 20

Inhibition of Cdk2 results in cell cycle arrest in ___ and ___.
Inhibition of Cdk1 results in arrest in ___.

Answer 20

G1 and S, G2

Question 21

In mammalian cells, ATM and Chk1 also mediate cell cycle arrest by the protein ___.

Answer 21

p53

Question 22

Chk1 phosphorylates p53, stabilizing it, leading to the expression of the protein ___ = An inhibitor of Cdk2/cyclin E.

Answer 22

p21

Question 23

Reminder: p21 is a ___ ___ (CKI)

Answer 23

Cdk inhibitor (CKI)

Question 24

The p53 gene is frequently mutated in human ___. Loss of p53 prevents cell cycle arrest in response to DNA damage, so the damaged DNA is replicated and passed on to daughter cells.

Answer 24

cancers