THE CELL CYCLE 2

Question 1

HOW DO GROWTH FACTORS STIMULATE
ENTRY INTO THE CELL CYCLE?

Answer 1

Growth factors bind to specific
cell-surface associated receptors.

Question 2

what happens the growth factor receptor upon binding?

Answer 2

its typically clustered or aggregated, due to multivalent nature of growth factors

Question 3

what does aggregation of the receptor facilitate? why?

Answer 3

transphosphorylation, due to an intrinsic kinase activity of the receptor.

Question 4

what does modifications to receptor cytoplasmic tail and the kinase properties allow for?

Answer 4

the recruitment and ability to act upon different molecules respetively.

Question 5

what does the growth factor signal ultimately activate a range of? what do these direct?

Answer 5

transcription factors to enter the nucleus. direct the battery of mRNAs required for cell division.

Question 6

what classes of genes do growth factors initiate the transcription of?

Answer 6

early response genes and delayed response genes.

Question 7

what are early response (ER) genes?

Answer 7

induced after 15 mins of receptor engagement and are protein synthesis independent.

Question 8

what are delayed response (DR) genes?

Answer 8

induced >1hr after receptor engagement, protein synthesis dependent

Question 9

what is the typical product of ER genes?

Answer 9

transcription factors.

Question 10

do cells in G0 exhibit synthesis of the products from either of these ER/DR stages?

Answer 10

little to none but induced to do so upon introduction of growth factors into the medium.

Question 11

name 3 ER products, what are they?

Answer 11

Myc, Fos and Jun. all of them are transcription factors.

Question 12

what does mutations in myc, fos and jun cause

Answer 12

malignant growth, uncontrolled expression leads to cells entering the cell cycle.

Question 13

what can cells that have defects in myc do?

Answer 13

if it is inactivated cell will not grow even with abundant growth factors. overexpression causes it to enter the cell cycle leading to apoptosis even without growth factors.

Question 14

what do ER gene products activate?

Answer 14

they activate transcription of DR gene products.

Question 15

what do DR genes code for?

Answer 15

proteins that pass the restriction point in the cell cycle.

Question 16

give 3 examples of DR gene products?

Answer 16

cyclins D and E, cyclin dependent kinase 2

Question 17

what is the epidermal growth factor pathway?

Answer 17

EGF pathway is a signaling pathway that responds to the EGF protein and ultimately promotes cell growth and division.

Question 18

what does RAS trigger in the EGF pathway?

Answer 18

cascade of protein interactions, leading to production of MAP kinase.

Question 19

what does son of sevenless do?

Answer 19

SOS acts as a GDP/GTP exchange factor for RAS. causes RAS to dissociate rapidly from GDP to GTP.

Question 20

what does overexpression of HER 2 have an association with? how is it treated?

Answer 20

increased
spontaneous receptor activation in
the tumor cells. with the monoclonal antibody herceptin.

Question 21

can integrins promote RAS activation?

Answer 21

yes.

Question 22

why is RAS commonly mutated in cancers?

Answer 22

pivotal role in growth factor receptor signalling.

Question 23

in cancers that have mutated RAS, where does RAS spend most of its time?

Answer 23

in the GTP bound state compared to the GDP state.

Question 24

what percent of cancers have RAS mutations? where do they mostly occur?

Answer 24

30%. most at position 12 and 13.

Question 25

what is major difference between somatic and cells in embryonic development?

Answer 25

embryos undergo rapid DNA replication and cleavage without doubling the cells content, called the blastula stage.

Question 26

what is eliminated essentially in embryonic development ?

Answer 26

the G1 and G2 stages.

Question 27

experimental approaches in cell cycle research?

Answer 27

cell synchronisation, centrifugal elutration, flow cytometry analysis

Question 28

what conclusions were drawn from isolating relatively pure populations of cells at distinct points in the cycle and fusing
them with cells of the same type

Answer 28

1. Mitosis is dominant over all other phases of the cell cycle.
2. S-phase contains factors that stimulate DNA replication in a G1 nucleus
   but not in a G2 nucleus.

Question 29

what is the nature of the factors that exist in the different phases of the cell
cycle?

Answer 29

cyclins and cyclin dependent kinases.