Exam 2 Flashcards
(107 cards)
1
Q
Interphase
A
Nucleus is visible and cell function occur
G1, S, G2
2
Q
G1
A
btw cytokinesis and S phase
Chr are single
new organelles are formed
cell grows in size
3
Q
Restriction point
A
G1-S transition
commitment to DNA replication and division
Can put cell in G0
4
Q
G0
A
Resting phase. Quiescent or Senescent
5
Q
Quiescent
A
Reversible. lack of cell growth signals
growth inhibitory signals (TGFBeta)
DNA dmg detected by p53
6
Q
Senescent
A
Irreversible. telemoere shortening
still can function. alt to apop
7
Q
S phase
A
DNA replicates
Sister chromatid remain together
8
Q
G2
A
Prepares for mitosis
9
Q
M phase
A
Mitosis
Prophase, metaphase, anaphase, telophase
10
Q
G1/S
A
DNA damage checkpoint: S phase blocked
11
Q
G2/M
A
checks if replication is complete
12
Q
SAC
A
Anaphase blocked if chromatds are not properly assembled on mitotic spindle
13
Q
CDKs
A
Cyclin dependent protiens
Ser/Thr
activated by binding to cyclin
14
Q
CK4/6
A
Cyclin D - G1 pase
15
Q
CDK2
A
Cyclin E - G1/S
Cyclin A - S
16
Q
CDK1
A
Cyclin A - S/G2
Cyclin B - M
17
Q
Inhibitors for CDK-Cyclin Activity
A
D-CDK4/6 = p16,p15,p18,p19
Cyclin E,A,B = p21,p27,p21
18
Q
TGF beta
A
Induces p15 and p21
19
Q
p53
A
inhibits through p21
20
Q
pRb
A
inhibits cell cycle at R pt - binds to E2F
extensive phosphorylation of RB allows cell cycle progression
Cyclin D-CDK and Cyclin E-CDK control phosphorylation
21
Q
Mitosis promoting Factor (MPF)
A
G2-M transition
Cyclin B combines with CDK1 = MPF
reaches critical lvl at end of G2 and counts to peak through M
Activates Anaphase promoting complex (AC/C)
22
Q
SAC
A
Spindle assemble checkpoint
INhibits APC/C until CHR aligned on metaphase plate and checks kinetochores
23
Q
4 modes of cell singaling
A
Endocrine = insulin
Paracrine = GF
Synpatic = AcH
Contact Dependent = Notch
24
Q
Growth Factors
A
molecules released by cell that signal other cells
promote differentiation and maturation
25
Cytokines
proteins involved in immune response
26
Hormones
proteins, steriods, fatty acid derivatives produced by endocrine glands (long range)
27
Enzyme - coupled receptors
act as enzymes/ assosiate with enzymes in the cell
Control cell growth, proliferation, differentiation, survival
Ligands
28
Receptor - Tyrosine kinases (RTKs)
enzyme coupled
3 domains = Extracellular, Transmembrane, Cytoplasmic
Activates Ras, PI-3K
29
Dimer
2 receptor molecules associate
30
PI-3K signlaing
promotes cell survival
31
PI-3K works
1) PI3K binds to RTK and phosphorylates
2) PI-33k Phosporylates PIP2 which makes PIP3
3) PIPs recruit Akt and PDK1
4) PDK1 and mTor phosphorylate Akt
5) Akt released into cytosol where activates other intracellular proteins
6) Akt activates Bad, pro-apoptotic protein
7) Bcl2 released and promotes cell survival
32
PTEN
dephosphorylates PIP3
Tumor Supressor
men with prostate cancer have lost this
33
Mechanisms for targeting growth factor receptors
Downstream pathways
anti-ligand
Anti receptor
Receptor inhibitor
34
Anti ligand
use antibodies to target ligand
35
Anti receptor
use antibodies target the RTK
36
Receptor inhibitor
molecule inhibitor of RTK to reduce activity
37
HER2
gene encoding for RTK
| overexpressed in breast cancer
38
Herceptin (traztuzibmab)
HER2 therapy
blocks downstam HER2
Flags HER2+ cells for destruction
39
Signal diversity
receptors activate multiple intracellular pathways
| multiple effects of one signal receptor
40
Cross talk
pathways regulated by other pathways
41
Redundancy
pathways activated by more than one receptor
| Diff signals but similar effects
42
Signal amplification
multiple steps in pathway allows for signal to be amplified
| small amt of ligand = big effects
43
Apoptosis
```
programmed cell death/cell suicide
Orderly
cells into parcels
plasma memb remains inact
recycle parts
Reponse to genomic dmg
anoxia
signaling imbalances
```
44
Atrophy
too much cell death
| Parkinson's and alzheimer's
45
Hyperplasia
Not enough cell death
| Cancer
46
Necrosis
response to toxxic chemical/physical injury
messy
leaks cellular components
causes immune response
47
Morphological changes in apoptosis
Pyknosis
memb blebbing
rounding of cell
reduction of cell vol
48
Pyknosis
chromatin condensation
| nucleus collapsed into dense structure due to chromatin condensation
49
Anoxia
oxygen deprivation
50
Blebs
patches of plasma memb extrude
51
Apoptotic bodies
cell broken up into small fragments
| Memb bound
52
Phophatidylserine
membrane protein flips out from inner layers, signals macrophage
53
3 pathways lead to apoptosis
Extrinsic - death ligand
Intrinsic - radiation,toxins
Perforin/granzyme - cytotoxic t cells
54
Caspasses
family of cysteine aspartyl-specififc protease enzymes that cleave proteins after an aspartic acid
55
Initiator
initiate apaoptosis by cleaving other caspases
56
Executioner
cleave multiple structural and repair proteins
57
Bcl2 Family protiens
Pro apoptotic
Pro survival
fate of cell determined by these
58
Pro-Apoptotic
promote release of cytochrome c from mitochondria
59
Pro-Survival
block release of cytochrome c from mitochondria
60
Apoptosome
complex of cytochrom c and Apaf-1
| Activates caspase-3
61
Cancer reciprocal translocations
Between chromosomes 14 and 18
| causes BCL-2 to come under control of constitutive promotor
62
Treatment of Apaptosis in cancer
Bcl-2 inhibitors
p53 activation
IAP inhibitors
63
Potential threats to geonme stability
```
Errors by DNA pol
Errors by MMR enzy
Double strand breaks
Incorporation of chemically altered nucleotides
Attack from mutatgens
Defects in DNA repair
```
64
Mismatch repair enzymes
monitor recently synthesized DNA to detect errors
65
Satellite
highly repeated sequences 100+ nuc
66
Microsatellites
highly repeated sequences that are short
67
Microsatellite Instability
expansion or shrinkage in regions of repeated nucleotides
68
Replication fork
Vulnerable to breakages
| Considered a DB strand break even when one strand breaks only
69
Exogenous Mutagens
Reactive oxygen species
Superoxide ions
Hyrdrogen peroxise
radicals
70
Depurination
spontaneous loss of purine base
71
Depyrimidination
spontanrous loss of pyrimidine
72
Deammination
Loss of amine group protrudine from guanine adenine and cytosine
73
Transition Mutation
one pyrimidine replaces another pyrimidine
74
Transversion
putine replacing pyrimidine vice versa
75
UV irradiation
produces cross links between adjacent pyrimidine bases
76
Alkylating agents
add alkyl group through covalent attachment
Used as chemotherapy
destabilizes bonds
77
DNA adducts
Chemical entity formed after reaction of carcinogen with DNA base
78
Aflatoxin B1 (AFB1)
Exogenous carcinogen produced by molds
79
Heterocyclic Amines
Arise from cooking foods at high temperatures
80
Defenses against mutagens
Physical shield
Enzymes including superoxide dismutase
repair enzymes
Free radical scavengers (vitamin C)
81
Repair Enzymes fix altered DNA
Dealkylating enzyme
Base excision repair
Nucleotide excision repair
82
Error prone repair
occurs when DNA replication fork encounters a still unrepaired DNA lesion
83
dsDNA repair
Homologydirected repair
| Nonhomologous end joining
84
Caretakers
maintenance of genomic integrity
85
Gate-keepers
Tumor Supressors
86
BRCA
germline mutations that increase risk of cancer
Chromosomal trnaslocations
Chromatid breaks
Triradial chromosomes
87
Chromosome Instability
Changes in chromosome number
88
Merotelic Attachment
kinetochore attached to two spindle poles
89
Centrosomes
organize microtubules in mitotic spindle commonly amplified in cancer cells
Targeting these can kill cancer cells
90
Tumor Progression
process by which normal cells evolve with increasingly neoplastic phenotypes
91
Multistep tumorigenesis
concept that carcinogenesis takes place in discrete stepes
92
Andeonmas (polyps)
precursors to carcinoma
93
Familial adenomatous polposis (FAP)
if have = colon carcinoma
| Inherit mutation in TS APC on chr 5
94
P and Q arms
Submetacentric
Metcentric
Telocentric
Acrocentric
95
Field Cancerization
Multiple apperently independent tumor arise in same organ
Sep. by normal epithelium
Poised for cancer prog
96
Tumorigenesis
Succession of clonal expansions
97
Darwininan Evolution
Individual cells compete with one another
random mutations create variation
FAvor proliferation and survival
98
Stochastic/Clonal Evolution model
Accumilation of mutations enhances resistance and fitness of tumor cells
All cells have similar chance in becoming a tumor
99
Intra-Tumor Heterogeneity
Tumor genomes become increasingly unstable
| Rate of mutation soars with each gen
100
Cancer Stem Cell Model
| Hierarchical Model
Some types of cancer have subpopulation of stem cells in tumor
Stem cells are not differentiated and are capable of self renewal
Stem cells can induce tumor similar to themselves
101
5 Pathway alterations
| Human cells highly resistant to transformation
```
Pathway
Ras
pRb
p53
Telomeres
PP2A
```
102
Driver mutations
give cell growth advantage
103
Passenger mutations
other mutations already in the cell
104
Skin carcinoma in mice
```
Initiator = stable long live mark
Promoter = repeat exposures cause inc prolif and is dose depenent
```
105
Tumor Latency
Time btw initiation and development of detectable tumor
106
Tumor promoters
Chronic inflamation
| Mitogenic agents
107
Complete Carcinogens
Act as initiator and promoter
