Cell Cycle Control Flashcards Preview

BMS > Cell Cycle Control > Flashcards

Flashcards in Cell Cycle Control Deck (98):
1

Can be the basis of many different medical disorders including autism, cataracts, and other congenital disorders, but the most significant is cancer

Deregulated cell growth

2

The basis of cancer

Deregulated cell growth

3

Accounts for nearly one quarter of the deaths in the US, and is exceeded only by heart diseases

Cancer

4

Will be the most frequently diagnosed cancers
in men and women, respectively, followed by lung and colorectal cancers both in men and in women.

Prostate and Breast cancer

5

Complex network of regulatory proteins that governs
DNA replication and segregation of chromosomes
through an ordered series of biochemical switches

Cell cycle control system

6

The cell cycle is a network of

Positive and negative feedback loops

7

The cell cycle MUST occur in a particular

Order

8

The cell cycle is controlled by a series of

-Serve as the point of no return

Biochemical switches

9

Once the biochemical switch is on, the cell must proceed to the

Next point

10

What are the two types of controls that regulate the cell cycle?

Internal and external

11

Monitors progression through the cell cycle so that each step happens in succession and delays later events until previous ones re completed

Internal cell cycle control

12

Cells respond to environmental signals in order to stimulate cell division when more cells are needed and to block cell division when no cells are needed

External cell cycle control

13

Function within the cell to ensure the correct progression of cell cycle events

Internal controls

14

Allow cells to respond to both positive and negative environmental cues

External controls

15

Defines the process where a cell duplicates itself and divides to make 2 daughter cells

-passes on IDENTICAL genetic information to daughter cells

Cell cycle

16

The cell duplicates itself during

S phase

17

The cell produces the two daughter cells during

M phase

18

M phase is separated in to which 2 stages?

1.) Mitosis
2.) Cytokinesis

19

Nuclear division of the cell

-goes from prophase to telophase

Mitosis

20

Cytoplasmic division into two daughter cells

-the last part of telophase

Cytokinesis

21

Interphase is all of the cell cycle that is not the M phase, and is made up of

G1, S, and G2 phases

22

Time delay for cell to grow (accumulate mass) and monitor intra- and extra- conditions

G1 and G2 phases

23

A point that exists at the end of G1 that measures the favorability of the environment

Restriction point

24

Once cells pass through the restriction point, they are committed to

DNA replication

25

If the environmental signals become unfavorable AFTER the restriction point is passed, can the cell stop DNA replication?

No

26

What happens if the environmental conditions are unfavorable at the restriction point?

Cells are arrested in G0 until conditions become favorable

27

Allows the cell cycle to keep progressing forward and initiate the cellular events required for each step of the cell cycle

Regulated production/activation of proteins at specific times

28

Triggers mitosis machinery

Assembly of mitotic spindle

29

Cell cycle progression is controlled by the sequential activation of a set of kinases called

Cyclin dependent kinases (Cdks)

30

Phosphorylate different proteins at different times in the cell cycle, which then initiates or regulates key events in the cell cycle

Cyclin-dependent kinases (Cdks)

31

For activity, Cdks are dependent on other proteins called

Cyclins

32

The activity of these kinases increase or decrease during different phases of the cell cycle

Cdks

33

Different cyclins exist for different phases of the

Cell cycle

34

Cyclins bind to their partner Cdks, activating the Cdks kinase activity, enabling them to phosphorylate downstream targets. Once this is accomplished, what happens?

Cyclins are degraded and Cdks are thus inactivated

35

What are the four classes of Cdks?

1.) G1 Cdk
2.) G1/S Cdk
3.) S Cdk
4.) M Cdk

36

Promotes passage through the restriction point

G1 Cdk

37

Commits cell to replication

G1/S Cdk

38

Initiates replication

S Cdk

39

Promotes mitosis

M Cdk

40

Act as the molecular switches of the cell cycle

Cyclin-Cdk complexes

41

An important aspect of the cell cycle is to inactivate the Cdk-cyclin complexes to ensure that each cellular event is triggered only

Once per cell cycle

42

Functions to conrtol the initiation of DNA replication once per cell cycle at replication origins

S-Cdk

43

A large multi-protein complex binds to the origins of replication. There are called the

Origin Recognition Complex (ORC)

44

Bind to origins throughout the cell and act as landing pads for other regulatory proteins to initiate replication at different positions throughout the genome

Origin Recognition Complex (ORC)

45

What is part one of the control of initiation of replication or entry into S phase?

Cdc6

46

Cdc6 is usually present at low levels throughout the cell cycle. but increases transiently in

Early G1

47

Binds to ORCs, which in turn causes recruitment of the Mcm proteins

Cdc6

48

What types of proteins are the Mcm proteins?

Helicases

49

All together, the ORC, Cdc6, and Mcm complex is called the

Pre-replicative complex (pre-RC)

50

Functions to have the pre-RC poised to replicate the DNA

Cdc6

51

Triggers replication by assembling DNA polymerase at the origin and activating the Mcm proteins

S-Cdk

52

What is part two of the control of initiation of replication or entry into S phase?

S-Cyclin

53

After Cdc6's activity, the origin is now ready to fire, but it requires the activity of

S-Cdk

54

S-cyclin transcription is activated in

Late G1

55

Forms and activates S-Cdk, which then phosphorylates the pre-RC, activating replication

S-cyclin-Cdk complex

56

Also prevents the re-replication of DNA. This is an example of one of the checks and balances that is important for cell control

S-Cdk

57

Causes Cdc6 to dissociate from ORC after origin has fired for replication

-results in disassembly of pre-RC

Phosphorylation of Cdc6 by S-Cdk

58

The dissociation and phosphorylation of Cdc6 from the ORC also causes its

Degredation

59

Also phosphorylates Mcm/helicase proteins and causes their export from the nucleus

S-Cdk

60

S-Cdk activity remains high during G2 and mitosis causing the Cdc6 protein to always be phosphorylated, therefore preventing

Re-replication

61

Also ensures no re-replication by also phosphorylating Cdc6 and Mcm proteins

M-Cdk

62

To allow replication at the end of a cell cycle, all Cdk activity is reduced to zero at the end of

Mitosis

63

Similar to S phase, the M phase is poised and ready to go. It is activated by

M-Cdk

64

The regulation of M-Cdk is controlled by which three proteins?

1.) M cyclin
2.) Cdk Activating Kinase (CAK)
3.) Cdk Inhibitory Kinase (Wee1)

65

Gradually increases during G2 and M phases due to transcription of the gene

M Cyclin

66

When M cyclin binds M-Cdk, the complex is only partially active. It become fully active after phosphorylation by

Cdk-activating kinase (CAK)

67

Only partially activate Cdks

Cyclins

68

When M cyclin binds M-Cdk, the complex is only partially active. It become fully active after phosphorylation by CAK. Before the complex can do anything, it is inactivated by

Cdk-inhibitory kinase (Wee1)

69

Removes the inhibitory phosphate added by Wee1 and re-activates the complex

-Shows how the M-Cdk complex is poised for activation

Cdc25

70

The M-Cdk compex contains a cyclin, and activating phosphate (from CAK) and an inhibitory phosphate (from Wee1). It is activated when the phosphate from Wee1 is cleaved by Cdc25. This shows how the M-Cdk complex is

Poised for activation

71

When the M-Cdk complex is active, it phosphorylates and activates proteins that are important in

Assembly of mitotic spindle, chromosome condensation, and breakdown of nuclear envelope

72

One feedback loop that enables more M-Cdk to become activated is that active M-Cdk inhibits

Wee1

-prevents inhibition of other M-Cdk's

73

Another feedback loop that enables more M-Cdk to become activated is that active M-Cdk phosphorylates more

Cdc25

-activates more of the phosphatase and leads to more active M-Cdk

74

Exit from mitosis requires inactivation of M-Cdk, which occurs primarily through protein degradation by

Ubiquitination

75

The protein that causes M-Cdk degradation is a ubiquitin ligase called

Anaphase Promoting Complex (APC)

76

APC is activated by

-A negative feedback loop

Active M-Cdk

77

A phase with absolutely no Cdk activity

G1

78

What are the three mechanisms to ensure that there is no Cdk activity in G1?

1.) Ubiquitin mediated degradation of Cdks
2.) Cyclin Kinase Inhibitor (CKI) accumulation
3.) Decreased Cyclin Transport

79

In animal cells, decreased cyclin transport is mediated by the

Retinoblastoma (Rb) protein and the E2F transcription factor

80

Bind to Cdk-Cyclin complexes and inhibit their activity

Cdk Inhibitor Proteins (CKIs)

81

CKI production is increased during

G1

82

A transcription factor that reglates the expression of many genes required for entry into S phase including
G1/S and S cyclins

E2F

83

E2F function is controlled in part by the

-binds E2F during G1 and blocks its activity

Rb Protein

84

Rb binding E2F during G1 results in downstream genes (i.e. G1/S and S cyclins) not being

Transcribed

85

When cells receive and extra-cellular signal to divide, G1-Cdk accumulates and

-reduces affinity of Rb for E2F, which prevents inhibition

Phosphorylates Rb

86

Phosphorylates Rb, reducing its affinity to E2F. This then results in the
expression of G1/S and S cyclin

G1-Cdk

87

Loss of both copies of the Rb gene leads to

Retinoblastoma

88

Increases its own expression once released by Rb inactivation

-positive feedback

E2F

89

E2F expression leads to production of

-phosphorylates more Rb, thereby releasing more E2F

G1/S-Cdk and S-Cdk

90

The increase in G1/S-Cdk and S-Cdk causes the phosphorylation and destruction of

-activates more G1/S-Cdk and S-Cdk

Ubiquitin ligases and CKIs

91

The function of the cell cycle is to transmit IDENTICAL genetic information to the daughter cells so that there is not an accumulation of

Somatic mutations

92

There are 2 checkpoints in the cell cycle to make sure that DNA is ok. These occur in

Late G1 and Late G2

93

In G2, if the DNA is damaged then this sends a signal that blocks

Cdc25 activation

94

What happens when activation of Cdc25 is blocked by the G2 checkpoint?

M-Cdk is not activates and cell does not progress to mitosis

95

The G1 checkpoint prevents progression into S phase by inhibiting the activation of

G1/S-Cdk and S-Cdk complexes

96

The activity of the G1 checkpoint is controlled in part by

p53

97

Stimulates the expression of several genes including the CKI protein p21

p53

98

The CKI then binds G1/S-Cdk and S-Cdk and inactivates them, which

Prevents passing of the restriction point

-No S phase entry

Decks in BMS Class (62):