Cancer II 2 Flashcards
1
Q
p53 can induce apoptosis in two different ways
A
- transcribes pro-apoptotic bcl-2 proteins
acts at mitochondrial membrane - directly binds to and 2. inhibits anti-apoptotic bcl-2 proteins
2
Q
p53 is constantly
A
expressed in cells
3
Q
under normal circumstances p53 is degraded by
A
MDM2
4
Q
DNA damage what happens to p53
A
phosphorylated so MDM2 can’t bind to it
5
Q
Mdm2 is
A
normal inhibitor of p53
so it is a proto-oncogene
6
Q
kinase that can phosphorylate p53
A
ATM
7
Q
ATM involved in which syndrome
A
ataxia Telangiectasia
AR
8
Q
draw out pathway with dna damage and how p53 gets activated by it
A
43
9
Q
p53 transcribes what to stop cell cycle
A
p21
10
Q
if there are high levels of p53, and after cell cycle is stopped p53 levels continue to increase, what happens
A
it maks pro apoptotic
11
Q
what does arf inhibit
A
mdm2
12
Q
E1A
A
adenoviral oncogene that triggers excessive proliferation
13
Q
E1A, c-myc, ras result in release of
A
release of E2F
14
Q
E2F is involved in transcribing
A
transcribing cyclin E
15
Q
if there are really high levels of oncogenic signaling, what happens with E2F
A
more active than usual
16
Q
if there are really high levels of E2F it will transcribe
A
p14ARF
17
Q
p14ARF inhibits
A
MDM2
18
Q
ultimately what does p14ARF do
A
allows accumulation of p53 without phosphorylation
p53 doesn’t need to be phosphorylated because MDM2 is being inhibited
19
Q
draw out cycle starting with E1A, cmyc and ras
A
pg 45
20
Q
excessive myc production means theres a lot of
A
cyclin d being produced, ultiamtely a lto of E2F
21
Q
MDM2 inhibits
A
p53
22
Q
p14 arf inhibits
A
MDM2
23
Q
p14arf indireclty allows activation of
A
p53
24
Q
target genes for p53
A
p21
bax
dna repair enzymes
25
p53 involved in apoptosis through what method
transcriptional regulation
| inhibits the anti-apoptotic genes
26
one of the mechanisms of apoptosis (intrinsic) is initiated by what in mitochondria
pore formation of outer membrane of mitochondria
27
once pore is formed in mitochonrdia what happens4
cytochrome c goes in and trigers apoptosis
28
bak and bax form
homeodoimers
29
bcl-2 is what kind of protein
anti-apoptotic protein
30
bak and bax are
pro-apoptotic proteins
31
p53 can heterodimerize with
bcl-2 to inhibit it - so bcl-2 can't bind to bak or bax and therefore bak or bax will homodimerize and form pores
32
Rb is inhibitor of
E2F
33
p15 and p16 are
INK4 inhibitors of kinase 4
34
TGF beta pathway ultimately leads to increase of
p15 & p16
35
cyclin b cdk1 is
m phase cyclin
36
when is cyclin b cdk 1 expressed
all throughout G2 phase
37
cyclin b cdk1 is expressed through all of g2 cycle but only activated
when it goes from g2 into m phase
38
cyclin b cdk 1 also called
m cyclin
| MPF
39
cyclin b is being produced all throughout
g2
40
cyclin b binds to
cdk1
41
two kinases active in regulating M-Cdk (Cyclin B CDK1)
wee 1
| cdc25
42
cyclin b cdk 1 complex phosphorylated
2x
43
cdk activating kinase is
activating the complex cyclin b cdk 1 complex
44
wee1 kinase is
inactivating complex cyclin b cdk 1 complex
45
draw pathway for cyclin b cdk 1 complex in g2 phase
pg 54
46
when cell is ready to go into m phase there is activation of
cdc25
47
cdc25 is a
phosphatase
48
cdc25 does what
removes inhibitory phosphate group on cyclin b cdk 1 complex put on by wee1
49
cak stands for
cdk activating kinase
50
as son as cell is ready to go from g2 into m
cdc25 removes all the phosphates put on by wee1 on cyclin b cdk 1 complex and then it quickly goes into mitosis
51
explain how chromatin condensation, etc, stuff that is needed for mitosis is initiated
activated cyclin B CDK/1 complex phosphorylates the proteins associated w/ chromatin leading to condesnation of genome, etc, all the stuff needed for mitosis
52
what takes the cell through the initial phases of mitosis up to metaphase
cyclin B CDK-1 complex
53
chrom are maximally condensed by the time they are in
metaphase
54
before mitosis there is duplication of
centrosome
55
from two what do microtubule spindle radiate out from
centrosome
56
activation of m cyclin complex leads cell through
initial stages of mitosis up to metaphase
57
to go from metaphase to anaphase
there is a checkpoint
| need to have activation of APC/C
58
what needs to be active to get from metaphase to anaphase
APC/C
59
APC/C stands for
anaphase-promoting complex
60
ubiquitin ligases causes degradation of inhibitor of
separases
61
separases what are they
enzymes that proteolytically cleave the interactions b/w sister chromatids
62
separases function
separate sister chromatid allowing them to be pulled apart to separate poles
63
without metaphse to anaphse checkpoint could end up with
aneuploidy
64
mad2 function
sense if all sister chromatids are boudn to microtubule spindle
if they aren't lined up prevents apc/c so it doesn't go into anaphse until its ready
65
mad 2 prevents activation of
apc/c
66
telophase
nuclear envelope reforms
67
in metaphase there is degradation of what and then activation of what
degradation of all the cyclin CDK complexes, activation of APC/C
68
activation of APC/C allows cell to go from
metaphase to anaphase
69
is there inflammation with apopt.
no
70
when cells are apoptotic they split into
apoptotic bodies
71
when cell is apoptotic what is flipped
phosphotidyl serine is flipped to outer leaflet, "eat me" to macrophages
72
necrosis vs apoptosis
necrosis has inflammation
73
when is apoptosis important in development
limb formation, dies so we get fingers, etc.
| hollow structures
74
describe some things that happen to the cell during apoptosis
Phosphatidylserine translocated from cytoplasmic leaflet to extracellular leaflet of plasma membrane
Membrane “blebbing”: Cell contents not released, little inflammation
Loss of substrate attachment, rounded phenotype
Decrease in cell volume
Depolarization of mitochondrial membrane potential
Activation of caspases (cysteine proteases),
Endonuclease activation DNA degradation, RNA also degraded
Chromatin condensation forming crescent bodies
75
annexin
binds to phosphotidyl serine so you can see cells that are apoptotic
used in labs
76
two apoptotic pathway
intrinsic (mitochondrial pathwya)
| extrinisic pathway
77
death receptor function as
trimers
78
DR stands for
death receptor
79
FAS and TNFR1 are
death receptors
80
death receptors all have
death domain
81
death receptors all function as
trimers
82
when signaling molecule from outside binds to death receptors it causes
FADD binds to receptor which recruits pro-caspase-8 which results in cleavage of pro-caspase 8 into caspase 8
83
FADD
fast associated death domain protein
84
what is major caspase of extrinsic pathway
caspase 8
85
caspase cascade
when one pro-caspase cleaved and activated it will go cleave and activate another caspase
86
caspases are present in cell as
pro-caspases (inactive)
87
one pro-caspases needs to do what to get active
cleaved
88
caspase 8 will do what
cleave and activate effector capases (3, 6, 7) and those will digest the cell
89
caspase 3 6 and 7 do what
digest the cell
90
draw out extrinsic receptor mediated pathway
pg 76
91
caspase 3, 6, and 7 are also known as
executioner caspases
92
caspases 3 6 and 7 also cleave the ihibitor of an
endonuclease (endoncleases are activated to start digesting the genome)
93
DISC stands for
death inducing signaling complex
94
formation of disc activates
pro-caspase 8
95
intrinsic apoptotic pathway is also known as
mitochonrdial pathway
96
what initiates the intrinsic pathway
pore formation in outer membrane of mitochondria
97
what is initiater caspase for intrinsic pathway
pro-caspase 9
98
cytochrom c binds to
apaf-1
99
binding of cytochrome c to apaf-1 forms what complex
apoptosome
100
apoptosome activates
caspase 9
101
caspase 9 will
cleave and activate effector caspase 3, 6, 7
102
extrinsic and intrinsic pathway are identical once
effector caspases are active
103
caspase 3, 6, 7 cleave
proteins w/in cell, everything gets digested incell
104
IAP stand for
inhibitors of apoptosis
105
IAP inhibit
executioner caspases
106
IAP what happens in cancer
over expressed - b/c they inhibit apopt.
107
smac/diablo protein inhibits
the inhibitors of apoptosis IAP
108
smac/diablo is
tumor supressor - promotes apoptosis by inhibitong inhibitors of apoptosis
109
apoptotic stimulus
pro formation in outer membrane of mitocrhondria
110
caspase 3 when activated
cleave the inhibitor of endonuclease
111
endonuclease activity with activation of
caspase 3
112
endonuclease will start
digesting genome
113
cell that is apoptotic will see what regarding dna
dna ladder
114
bcl-2 includes
pro-apoptotic and antiapoptoci
115
antiapoptic bcl-2 proteins
Bcl-2 and bcl-xl
116
pro-apoptotic bcl-2 proteins
bax, bad, bak, bid
117
anti-apoptotic genes are type of
oncogene
118
bax and bak direclty form
pores in outer membrane in mitochondria
119
bcl-2 and bcl-xl inhibit
bak and bax
120
bad and bid inhibit
bcl-2 and bcl-xl
121
in order to get pore formation in mitochondria need
bak or bax homodimerization
122
bcl-2 can heterodimerize with
| this does what
bak or bax
| prevents them from forming pores
123
bak and what do same thing
bax
124
bad and bid form heterodiers with
| this does what
bcl-2 or bcl-xl
| allows pore formation
125
pore formation result in release of
cytochrome c
126
caspase 8 also cleaves (beside executioner)
BID
127
BID when cleaved, releases
TBID
128
TBID stands for
truncated BID
129
TBID can heterodimerize with
bcl-2 or bcl-xl
130
TBID is
pro-apoptotic bcl-2 protein that gets activated following extrinsic pathway but stimulates intrinsic pathway
131
when there is dna damage what pathway will be activated
intrinsic apoptotic
132
smac mimetic
mimics what smac does
| drugs target cancer with overexpression of iap - they bind and inhibit iap
133
mimetic
drug that mimics
134
p53 promotes transcription of what pro-apoptotic proetins
bac and bax
135
p53 can heterodimerize with
bcl-2 bcl-xl
136
what other protein can bind and heterodimerize with bcl-2 and bcl-xl
TBID p53 bad
137
bcl-2 inhibits
bax
138
when p53 is around what does it do regarding bcl-xl
binds to bcl-xl so bax is free and can cause pore formation
139
draw pathway for p53 and the intrinsic pathway
pg 94
140
draw pi3k and akt, pten pathway
pg 97 98 99
141
is p14 arft a proto-oncogene or tumor suppressor gene
tumor suppressor gene - it's allowing accumulation of p53 through inhibiting its inhibit mdm2
142
what makes arf
E2F
143
pore formation is induced by what genes
pro-apoptotic bcl-2 genes
144
What are the two HPV oncoproteins
E6 & E7
145
How does HPV oncoprotein E6 cause cancer
degrades p53
146
How does HPV oncoprotein E7 cause cancer
binds & inhibits Rb
