Cell growth regulation

Question 1

What are mitogens?

Answer 1

Proteins that stimulate proliferation

Question 2

what are paracrine proteins?

Answer 2

produced locally to stimulate proliferation of a different cell type that
has the appropriate cell surface receptor

Question 3

What are autocrine proteins?

Answer 3

Produced by a cell that also expresses the appropriate cell surface receptor

Question 4

What are endocrine proteins?

Answer 4

like conventional hormones, released systemically for distant effects

Question 5

Steps involved in DNA replication?

Answer 5

1. DNA is replicated semiconservatively (daughter cells
   inherit one parental and one new strand)
2. New DNA is synthesized in the 5’ to 3’ direction from
   deoxynucleotide triphosphate precursors at a
   replication fork by a multienzyme complex (a
   replication machine)
3. Fidelity is determined by base pairing (A=T, G≡C)
   and presence of a proof reading enzyme in DNA
   polymerase
4. Synthesis of the new DNA strand uses an RNA
   primer and occurs continuously on the leading strand
   and discontinuously on the trailing strand (giving rise
   to Okazaki fragments, which are ligated together after
   removal of the RNA primer)

Question 6

What are the steps involved in mitosis?

Answer 6

• Prophase (1)
  – Nucleus becomes less definite
  – Microtubular spindle apparatus assembles
  – Centrioles (yellow) migrate to poles
• Prometaphase
  – Nuclear membrane breaks down
  – Kinetochores attach to spindle in nuclear region
• Metaphase (2)
  – Chromosomes (blue) align in equatorial plane
• Anaphase (3)
  – Chromatids separate and migrate to opposite poles
• Telophase (4)
  – Daughter nuclei form
• Cytokinesis
  – Division of cytoplasm
  – Chromosomes decondense

Question 7

What are examples of S-phase active drugs?

Answer 7

• 5-flurouracil
• Bromodeoxyuridine

Question 8

What is 5-flurouracil?

Answer 8

an analogue of thymidine blocks thymidylate synthesis

Question 9

What is bromodeoxyuridine?

Answer 9

another analogue that
may be incorporated into DNA and detected
by antibodies to identify cells that have
passed through the S-phase

Question 10

What are examples of M-phase active drugs?

Answer 10

-Colchicine
-Vinca alkaloids
-Paclitaxel

Question 11

What does colchicine do?

Answer 11

stabilizes free tubulin, preventing microtubule polymerization and
arresting cells in mitosis – used in karyotype analysis

Question 12

What do vinca alkaloids do?

Answer 12

similar action to colchicine

Question 13

What does paclitaxel do?

Answer 13

Taxol, stabilizes microtubules, preventing de-polymerization

Question 14

What cell cycle drugs are used in cancer treatment?

Answer 14

5-Fluorouracil, paclitaxel, the vinca alkaloids and tamoxifen are used in treatment of cancer

Question 15

What do cell cycle controls ensure?

Answer 15

Controls (involving specific protein kinases and phosphatases)
ensure the strict alternation of mitosis and DNA replication

Question 16

How many genes do CDK catalytic subunits have?

Answer 16

10 genes

Question 17

How many genes do cyclin regulatory subunits have?

Answer 17

> 20 genes

Question 18

What do active cyclin-CDK complexes do?

Answer 18

Active Cyclin-CDK complex
Phosphorylates specific substrates

Question 19

What is the retinoblastoma protein key in?

Answer 19

The retinoblastoma protein is a key substrate of
G1 and G1/S cyclin-dependent kinases

Question 20

What does unphosphorylated retinoblastoma do?

Answer 20

Unphosphorylated RB binds E2F
preventing its stimulation of S-
phase protein expression

Question 21

What happens when retinoblastoma is phosphorylated?

Answer 21

Released E2F stimulates expression of more Cyclin E and
S-phase proteins e.g. DNA polymerase, thymidine kinase, PCNA etc.
DNA replication starts

Question 22

What are the 2 families of cyclin dependent kinase inhibitors?

Answer 22

1. CDK inhibitory protein/kinase inhibitory protein (CIP/KIP) family(now called CDKN1)
2. Inhibitor of kinase 4 family (INK4)(now called CDKN2))

Question 23

What is CDKN1 expression stimulated by?

Answer 23

Expression of members of this family stimulated weakly by TGF and strongly by DNA
damage (involving TP53)

Question 24

What do CDKN1 inhibit?

Answer 24

Inhibit all other CDK-cyclin complexes (late G1, G2 and M)

Question 25

What are CDKN1 gradually sequestered by?

Answer 25

Are gradually sequestered by G1 CDKs thus allowing activation of later CDKs

Question 26

What is the expression of CDKN2 stimulated by?

Answer 26

Expression stimulated by TGF-beta

Question 27

What do CDKN2 specifically inhibit?

Answer 27

Specifically inhibit G1 CDKs (e.g. CDK4 the kinase activated by growth factors)

Question 28

What induces cyclin expression?

Answer 28

Growth factors induce cyclin expression

Question 29

What does DNA damage detected at checkpoints trigger?

Answer 29

DNA damage detected at checkpoints
triggers cell cycle arrest or apoptosis

Question 30

What is the role of TP53 in response to DNA damage?

Answer 30

After kinase activation it leads to:
-DNA repair like excision repair
-If repair not possible then apoptosis
-Expresses CKI to induce cell cycle arrest

Question 31

What is TP53 destruction by?

Answer 31

TP53 destruction by proteasome