Cell Bio Lecture 35

Front 1

what is the primary determinant of the CDK activity? ***

Back 1

cyclins (concentration of protein)

Front 2

cyclin activity can be ____

Back 2

fine-tuned (other proteins affect its activity)

Front 3

these can both inhibit and activate

Back 3

kinases and phosphatases

Front 4

inhibitor proteins can also prevent the ____

Back 4

activation

Front 5

proteolysis can ____ and also act as a _____

Back 5

fine-tune and act as a checkpoint

Front 6

(what) targeted for destruction because

Back 6

we are adding on this globular multiubiquitin chain

Front 7

what do s-phase cyclin-cdk complexes (s-cdks) do?

Back 7

they initiate DNA replication once per cycle

Front 8

a cell in s-phase and another cell in g1 phase combine and what happens?

Back 8

the materials in s-phase were able to push g1 into s-phase which means both now are duplicating DNA

Front 9

what does s with g2 tell us?

Back 9

it is not enough to drive backwards (this tells us that there are block controls in place) g2-phase nucleus stays in g2, s-phase nucleus continues DNA replication

Front 10

what are blocks?

Back 10

they are objects that do not allow for backward movements

Front 11

g1 and g2 combined do not allow

Back 11

jumping forward
this tells us that this is a linear pathway or punctuated continuum that cannot skip a step as the S is in this example

Front 12

s-cdk phosphorylates proteins at ______ which initiates _____

Back 12

at DNA replication origin initiating DNA synthesis through a mechanism that ensure that the DNA is duplicated only once per cycle

Front 13

s-cdk triggers

Back 13

s-phase

Front 14

why cant you skip from g1 to g2

Back 14

because without s-cdk you cannot move forward
s-cdk triggers s-phase

Front 15

accessory proteins must be used to bind to complex and then ____

Back 15

accessory proteins (Cdc6) and then recruits a series of proteins (Mcm) which has now primed this whole structure

Front 16

in addition to s-cdk, there is m-cdk that also ___

Back 16

phosphorylates which prevents it from moving backwards

Front 17

m-cdk also helps ensure ____

Back 17

re-replication does not occur by phosphorylating Cdc6 and Mcm (also g1/s-cdks help with export)

Front 18

at the end of mitosis, all cdk activity in the cell is ____

Back 18

reduced to zero

Front 19

at the end of m, dephosphorylate of

Back 19

cdc6 and mcm proteins

Front 20

at the end of m allows pre-rc assembly to

Back 20

occur once again at g1/s transition

Front 21

at the end of M, you need to re-stock up but also need a

Back 21

phosphate

Front 22

____ both prevent going backwards by getting ride of ___ and cannot ___ until it receives a signal to do so

Back 22

degrading and phosphorylating both prevent going backwards by getting rid of everything it uses, and cannot re-stock until receives a signal to do so
-cannot duplicate DNA with separation
-makes sure everything goes back to zero, in part because of degradation

Front 23

activation of m-phase cyclin-cdk complexes (m-cdks) triggers

Back 23

entry into mitosis

Front 24

m-cdk activation leads to events of early mitosis, whereby

Back 24

cell assembles a mitotic spindle
-prepares for segregation of the duplicated chromosomes which consist of sister chromatids glued together

Front 25

active m-cdk has negative feedback on

Back 25

cdk-inhibitory kinase?

Front 26

cdc25+P ____

Back 26

cleaves off inhibitory phosphate and now active m-cdk which is able to inhibit its cdk-inhibitory kinase and activates phosphatase cdc25

Front 27

proteolysis triggers

Back 27

chromatid separation

Front 28

apc acts with another protein to cause

Back 28

ubiquitylation and proteolysis of m-cyclin which drives the cell irreversibly "forward" in cell cycle

Front 29

exit from mitosis requires eventual ___

Back 29

inactivation of M-cdk

Front 30

inactivation occurs mainly by

Back 30

ubiquitin proteolysis of M-cyclins

Front 31

thus activation of ____ leads not only to anaphase, but also _____

Back 31

activation of cdc20-APC complex leads to m-cdk inactivation

Front 32

m-cdk inactivation in turn leads to

Back 32

all of the other events that take the cell out of mitosis

Front 33

APC stands for and is held in inactive position until

Back 33

anaphase promoting complex is held in inactive position until activated by cdc20 and m-cdk

Front 34

when APC is activated, it can

Back 34

degrade securin

Front 35

why do we keep everything in the off position?

Back 35

so it is appropriate to clip (cleave)

Front 36

cleaving by ___ promotes ___

Back 36

cleaving by separase promotes anaphase

Front 37

spindle attachment point, if the sensor says ___

Back 37

yes you are properly boudn, otherwise you will not get cleavage

Front 38

a "brake" in the cell cycle

Back 38

Rb regulates progression thru G1 to S-phase initiation

Front 39

Rb stands for and ____

Back 39

retinal blasome
-allosteric shape change when g-cdk phosphorylates rb protein into inactived state

Front 40

what is the key part in this?

Back 40

active E2F

Front 41

cell size controls

Back 41

cell-cycle in yeast

Front 42

what happens to cell size without nutritional cell-cycle control

Back 42

cell size shrinks and mass of cell decreases over time

Front 43

cell size with nutritional cell-cycle control

Back 43

cell remains the same and mass is the same

Front 44

without nutritional control, rate ___

Back 44

remains the same

Front 45

if you have nutritional control, the rate

Back 45

results in a longer cell cycle

Front 46

____ in one of your checkpoints if cell continues over time but loses cell size

Back 46

mutation

Front 47

dna damage checkpoints

Back 47

p53
checkpoints:
late in g1
late in g2

Front 48

cell size controls

Back 48

cell-cycle in yeast

Front 49

what if damage is too severe to fix?

Back 49

in multicellular organisms, leads to apoptosis (cell death)

Front 50

x-rays penetrate into DNA causing ____

Back 50

protein kinase activation and phosphorylation of p53

Front 51

what happens to cell size without nutritional cell-cycle control

Back 51

cell size shrinks and mass of cell decreases over time

Front 52

active p53 binds to _____

Back 52

regulatory region of p21 gene

Front 53

cell size with nutritional cell-cycle control

Back 53

cell remains the same and mass is the same

Front 54

without nutritional control, rate ___

Back 54

remains the same

Front 55

if you have nutritional control, the rate

Back 55

results in a longer cell cycle

Front 56

____ in one of your checkpoints if cell continues over time but loses cell size

Back 56

mutation

Front 57

dna damage checkpoints

Back 57

p53
checkpoints:
late in g1
late in g2

Front 58

what if damage is too severe to fix?

Back 58

in multicellular organisms, leads to apoptosis (cell death)

Front 59

x-rays penetrate into DNA causing ____

Back 59

protein kinase activation and phosphorylation of p53

Front 60

active p53 binds to _____

Back 60

regulatory region of p21 gene

Front 61

p21 is the ___

Back 61

promoter region
-cdk inhibitor protein that turns active complexes inactive

Front 62

checkpoints in g1 are

Back 62

-unfavorable extracellular environment at g1-cdk
-dna damage (p53)
-excess mitogenic stimulation (p53)

Front 63

checkpoints in g2

Back 63

unreplicated dna
dna damage
both at cdc25

Front 64

checkpoints in end of M that affects?

Back 64

chromosome unattached to spindle
affects to APC

Front 65

questions at start/g1 checkpoint

Back 65

should we divide or not?

Front 66

questions at g2/m checkpoint

Back 66

is everything duplicated?
is DNA ok?

Front 67

questions at M-A checkpoint

Back 67

is the system ready mechanically

Front 68

initiation of replication checkpoint

Back 68

only one initiation phosphoryl events

Front 69

c-cki is regulated by

Back 69

p51

Front 70

what are the inhibitory kinases?

Back 70

wee and m-cki

Front 71

what purpose does cell death serve?

Back 71

apoptosis is important for development too

Front 72

if you did not have cell death, you would have

Back 72

webbed fingers

Front 73

apoptosis plays a structural role

Back 73

in case of frog, the tail wouldn't go away because no cell death

Front 74

what happens if cell is too damaged?

Back 74

cells won't divide

Front 75

apoptosis can destruct

Back 75

infected cells

Front 76

necrosis is

Back 76

not controlled (cellular contents are released, going to stimulate cell death all around it) affects cells around it (explosion)

Front 77

apoptosis is ___

Back 77

controlled cell death, imploding (doesn't affect cells around it)

Front 78

apoptosis depends on proteases called

Back 78

caspases

Front 79

activation is triggered by

Back 79

adaptor proteins that bring multiple copies of specific procaspases close together

Front 80

procaspase activation is activated by

Back 80

cleavage

Front 81

caspase cascade (one molecule of active caspase x) breaks into ___ by ____

Back 81

many molecules of active caspase Y
by cleavage of cytosolic protein

Front 82

many molecules of active caspase Y cleave by ____ into even more molecules of ____

Back 82

cleavage of nuclear lamin into even more molecules of active caspase Z

Front 83

what factors influence cell cycle in mammalian cells?

Back 83

-nutrient abundance
-cell density
-growth factors
-sensitivity to growth factor
-degree of attachment

Front 84

nutrient abundance

Back 84

serum deprivation prevents passage thru the G1 checkpoint

Front 85

cell density

Back 85

neighboring cells compete for GFs

Front 86

growth factors

Back 86

crucial, present in small amounts, highly specific

Front 87

sensitivity to growth factor

Back 87

only low concentrations required

Front 88

degree of attachment

Back 88

can dictate the probability of division

Front 89

extracellular controls: extracellular growth factors stimulate

Back 89

cell growth and "density dependent inhibition of cell division"

Front 90

confluent monolayer

Back 90

cells no longer proliferate

Front 91

what stimulates cell proliferation

Back 91

flow of medium