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Flashcards in Cell Cycle Deck (37):
1

Cell Cycle- an overview

Involves DNA replication followed by cellular division to yield two daughter cells

2

what does atypical cell cycles lead to?

Uncontrolled cellular proliferation (hallmarks of Cancer)

3

What group of people are cancer incidences high in and low?

High- African American males

Low- American Indian females

4

Proliferation and death throughout organism's life

In a growing organism, there is more proliferation than death

In an adult organism, cell proliferation and death are in balance

Most cells in an adult organism are cell-cycle arrested

5

Cancer represents an imbalance

Increased rate of proliferation

Decreases rate of cancer cell death

6

Differentiated cells in mature organs- divide or nah?

Examples: nerve cells, striated muscles, cardiomyocytes

DO NOT DIVIDE

7

Cells growing on demand- divide or nah?

Examples: fibroblasts for healing and stems cells for proliferation


DIVIDE

8

Blood Cell precursors- divide or nah? *in adults

Examples: Bone marrow, megakaryocytes, platelets, myeloid cells

DIVIDE

9

G0

The non-dividing phase of the cycle

-resting cells-

10

G0 --> G1

Exposure to mitogenic stimuli such as growth factors or metabolites allows some cells to move onto the cycle

11

G1

Cells are preparing for DNA replication thru growth and metabolism

12

S

DNA replication phase

13

G2

Cells activate enzymes needed for mitosis

14

Interphase

DNA replication takes place (S phase)

15

Prophase & Prometaphase

Chromosomes appear as two thin threads (the chromatids) held together by a centromere

Chromosomes begin to condense

Micro tubules are attached to centrioles on one side and to chromatids on the other

16

Metaphase

The chromatids migrate to the equatorial plane

17

Anaphase/telophase

Separation of 2 sister chromatids and cellular division (cytokinesis)

18

Megakaryocyte- Cell cycle

Skip late anaphase and cytokinesis

Result: polyploidy cell so it can fragment easily

19

Trophoblast- Cell cycle

Skips the late anaphase and cytokinesis phase

result is a polyploidy cell

20

Cancer Cells- cell cycle

Has uneven segregation of chromosomes

Results in uneuploid cells

21

Experimental approach to see how each phase of the cell cycle is regulated?

Isolate cells at each stage and use proteins to see how long each stage lasts

22

How does cyclin fluctuate between interphase and mitosis?

Increases linearly throughout interphase until mid mitosis, and then drops

Picked up again at next interphase

*other proteins increase linearly*

23

Which cyclins are bound to Cdk2?

Cyclin E or A

24

Which cyclins are bound to Cdk4 or Cdk6

Binds cyclin D

25

Which cyclins are bound to Cdc2

Binds cyclin B

26

Job of CDK

Once bound to cyclin --> phosphorylate so downstream targets which promote a specific cell cycle phase

27

Cyclin complex G2

Cdc2-cyclin B

28

CKI inhibition of Cyclins

Ie: p16, p21 p27

Binds to the cyclin-CDK complex and inactivated it

Elevated DKI can inhibit cell cycle progression

Elevated cyclins can further promote the cell cycle

29

Cyclin complex G1 and Inhibition

Beginning: CDK 4,6 with cyclin D

Inhibited by p16 (CKI and 16 kD)



End of G1: CDK2 with cyclin E

Inhibited by p21 and p27

30

Cyclin complex S and Inhibition

CDK 2 with Cyclin A

Inhibited by p27

31

What are the targets of Cyclin-CDK complexes?

The Rb protein is a tumor suppressor
Inhibitory, primary regulated thru transcription

Partners with nuclear factor (transcription factor) E2F

32

E2F pathway (normal)

E2F free of Rb is a potent activator of genes involved in DNA synthesis and S phase progression

33

E2F pathway (binded to Rb)

Cdk4-Cyclin D or Cdk6-Cyclin D is capable of phosphorylation get Rb

Cdk2-cyclin E further phosphorylate a Rb

Phosphorylate do Rb is unable to partner with E2F allowing E2F to bind to S phase gene promotors and activate them


34

How is the E2F/Rb pathway inhibited

By the CKIS- p16, p21, p27

35

Which cancers have D-type cyclins unregulated with a down regulation of p27?

Breast cancer, Colon cancer, Prostate cancer

*homogeneity: different levels for each --> some breast cancers will not have high D levels

36

Which cancers have the CKI p16 gene mutated or deleted?

Bladder
Deletion- 49%
Mutation- 6%

Pancreas
Deletion- 20%
Mutation-27%

37

Other cancers with mutated CKIs

T-ALL
Deletion- 57%
Mutation- 7%

Sporadic Melanoma
Deletion- 11%
Mutation- 9%