Exam 4: Cell Cycle Flashcards Preview

Biochemistry > Exam 4: Cell Cycle > Flashcards

Flashcards in Exam 4: Cell Cycle Deck (55):
1

M phase

Mitosis - cell divides into two daughter cells

2

Interphase

time between mitosis
G1, S, and G2 phases

3

G1 phase

growth period precedes DNA synthesis

4

S phase

DNA is replicated only one time
At end, each chromosome has two identical sister chromatids linked by centromere

5

G2 phase

Second period of growth that precedes cell division

6

G0

cells are differentiated and no longer dividing
exited cell cycle, some cells can re-enter cell cycle when stimulated

7

G1/S checkpoint

start or restriction point
cell determines if conditions are favorable for division

8

G2/M checkpoint

ensures that all DNA has been replicated

9

Metaphase/anaphase transition point

All chromosomes are evaluated to ensure they are attached to mitotic spindle

10

DNA damage checkpoint

throughout cell cycle, detects damage to DNA
Cells with damaged DNA arrest until repairs are made, if damage can't be repaired, cell enters apoptotic pathway

11

cyclin-dependent kinases (CDKs)

enzymes that function in association with regulatory subunits - cyclins
Active at different stages of cell cycle and regulate progression through phosphorylation of different protein targets

12

M phase uses what cyclin/CDK complex

Cyclin A/CDK1 and Cyclin B/CDK1

13

Mid G1 phase uses what cyclin/CDK complex

Cyclin D/CDK4 & 6

14

Late G1 phase uses what cyclin/CDK complex

Cyclin E/CDK2

15

S phase uses what cyclin/CDK complex

Cyclin A/CDK2

16

mitogenic signals

tissue-specific growth factors required to stimulate cell growth and division
Must overcome controls (like restriction point) in order to promote proliferation in most cells

17

Interactions between cell and extracellular matrix

promote cell division

18

Interactions between neighboring cells

inhibit cell division - contact inhibition

19

early response genes

genes transcribed in initial phase of cell, after adding growth factor

20

c-Fos transcription factor

early-response gene
stimulates transcription of the delayed-response genes (other transcription factors, mid-G1 cyclins & CDKs, late G1 cyclins)
transcription of c-Fos stimulated by MAP kinase cascade

21

growth factor binds to receptors containing

tyrosine kinase activity - triggers autophosphorylation of tyrosine residues, forms a docking site for other signaling molecules

22

GRB2

binds to phosphotyrosine residues on activated growth factor receptor
binds protein Sos, bringing it to cell membrane

23

Sos

brought to cell membrane by binding with GRB2 on growth factor receptor
interacts with Ras - promotes exchange of GDP to GTP activating Ras

24

Ras

small G-protein
inactive in GDP-bound form, active in GTP-bound form
Activated by Sos
Activates protein kinase Raf

25

Raf

protein kinase activated by active Ras
phosphorylates/activates MAP kinase kinase

26

MAP kinase kinase

activated by active Raf
phosphorylates/activates MAP kinase

27

MAP kinase

activated by MAP kinase kinase
enters nucleus and regulates transcription of many genes
stimulates c-Fos transcription, which leads to progression through restriction point

28

Rb (retinoblastoma protein)

binds to protein products of delayed-response genes, E2F proteins, act as transcriptional repressors & inhibit transcription

29

E2F proteins

protein products of delayed-response genes
transcription factors - activating transcription of many genes required for DNA replication
stimulate transcription of late G1 cyclin (cyclin E), S phase cyclin (cyclin A), S phase CDK (CDK2)
Inactive when bound to Rb

30

Cyclin D-CDK4/6

Mid G1 phase cyclin/CDK complex
Promotes cell cycle growth by phosphorylating Rb, causing dissociation from E2F & activating E2F for transcription of genes & readying cell for S phase
Late G1 phase cyclin/CDK complex (cyclin E-CDK2) produced

31

Cyclin E-CDK2

Late G1 phase cyclin/CDK complex
continues phosphorylation of Rb, promoting entry of cell into S phase
phosphorylates p27 triggers proteolysis of inhibitor & activation of Cyclin A-CDK2 complex

32

INK4 proteins

compete with cyclin D for binding to CDK 4/6, act as specific inhibitor of CDK 4/6 activity

33

p27 (KIP1)

inhibits cyclin A-CDK2 complex (keeps it in inhibitory state)
forms complex with cyclin A-CDK2 - frees complex when phosphorylated

34

Cyclin A-CDK2

S phase cyclin/CDK complex
inhibited by forming complex with p27 (phosphorylated by cyclin E-CDK2)
Also requires dephosphorylation of internal inhibitor to be activated
When activated, DNA replication can begin - phosphorylates components of origins of replication to promote initiation of DNA replication

35

Cyclin A/B-CDK1

M phase cyclin/CDK complex
held in inactive phase due to inhibitory phosphorylation of CDK 1 subunit until DNA replication is complete
Dephosphorylation activates complex - phosphorylates many substrates responsible for driving early part of mitosis (chromosome condensation, formation of mitotic spindle, and disassembly of nuclear membrane)

36

Anaphase promoting complex

activated by attachment of chomosomes to mitotic spindle
leads to degradation of cohesion complexes that hold sister chromatids together at centromere
polyubiquinates cyclin A & B after anaphase is complete

37

ATM

G2/M checkpoint
protein kinase detects replication forks - recognizes that DNA synthesis is still in progress
prevents dephosphorylation/activation of cyclin/CDK1 complexes
Also works with ATR as a DNA damage checkpoint; responds to double-stranded DNA breaks

38

inhibition of anaphase promoting complex

by protein factors that recognize kinetochores not associated with spindle

39

ATM/ATR

DNA damage checkpoints
inhibits phosphatases that normally dephosphorylate and activate cyclin/CDK2 and cyclin/CDK1 complexes - block progression of cell cycle
Phosphorylates/stabilizes p53

40

ATR

DNA damage checkpoint
activated by DNA damage caused by UV light and certain drugs

41

p53

transcription factor stabilized from phosphorylation by activation of ATM/ATR
Activates p21, which inhibits both cyclin/CDK1 and CDK2 complexes - prevents cell growth
Intrinsic activator of apoptosis

42

p21

inhibitor of cyclin-dependent kinases
inhibits both cyclin/CDK1 and cyclin/CDK2 complexes - blocks S phase and mitosis

43

Ataxia-telangiectasia

inherited disorder, difficulty in coordination of movement, small wide blood vessels, more susceptible to infection & chronic lung infections, leukemias, & lymphomas, highly sensitive to radiation exposure
Caused by mutation in gene encoding ATM - cell response to double strand DNA breaks is impaired

44

Apoptosis

programmed cell death
removes damaged or infected cells from body
normal cell turnover, embryonic development & functioning of immune system
key means by which cytotoxic chemicals in cancer therapy work
Chromosome condenses, cell shrinks in size, nuclear envelope breaks up, cell fragmentation and blebbing occur (forming apoptotic bodies, which are then phagocytosed)

45

tumor necrosis factor (TNF)

produced by macrophages & play role in cell death and tissue destruction - seen in chronic inflammatory diseases

46

Fas ligand

produced by natural killer cells and cytotoxic T-lymphocytes

47

caspases

family of proteases that are present as inactive precursors until apoptotic signal recieved
Initiator caspases activated by apoptotic signal and activate executioner caspases - hydrolyze cellular proteins & trigger DNA fragmentation

48

Bcl-2 family

family of proteins involved in apoptosis - proapoptotic proteins
PUMA, BID, BAX

49

Bcl-2

antiapoptotic protein
outer mitochondrial membrane protein
inhibits BAX

50

BAX

protein that can form a channel in mitochondrial outer membrane
when stimulated allows release of cytochrome c from mitochondria into cytoplasm

51

PUMA & BID

function to stimulate BAX activity

52

Apaf-1

when bound to cytochrome c (released from mitochondria by BAX) it oligomerizates - results in formation of apoptosome

53

apoptosome

formed by activation of Apaf-1 by cytochrome c
recruits and activates initiator caspase, caspace-9

54

Caspase-9

initiator caspase
activated by apoptosome
activates caspase-3, executioner caspase

55

Caspase-3

executioner caspase
activated by caspase-9
sets cell down path of programmed cell death