Block 4 Lectures Flashcards
(198 cards)
1
Q
What are the two main phases of the cell cycle?
A
Mitosis and Interphase
2
Q
What are the 3 phases of interphase?
Include a brief description
A
- G1- pd between completion of previous mitosis and the initiation of DNA synthesis for the next
- S- period of DNA synthesis for chromosome duplication
- G2- period between completion of DNA replication and M phase initiation
3
Q
What is the Go phase?
A
holds cells that exit G1 and are post mitotic and non-proliferating
4
Q
What are the 3 checkpoints of the cell cycle?
Include a brief description
A
- G1/S- check if cell large enough and has enough nutrients
- G2/M- check if DNA replicated correctly and environment favorable
- Spindle Assembly/Anaphase- are chromosomes correctly attached to the spindle?
5
Q
What does a P13K pathway do?
A
drives cell growth
6
Q
Explain the P13K pathway
A
A growth factor activates the receptor tyrosine kinases to recruit and activate P13K at plasma membrane. P13K then binds to phosphotyrisine residues in cytoplasmic domains and generates P1(3,4,5)P3 to activate Akt which activates the protein kinase mTOR
7
Q
What does mTOR phosphorylate in the P13K pathway? (2)
A
- S6-kinase which phosphorylates S6 which increases translation of mRNA
- 4E-BP which releases elF4E from inhibition position which initiates translation
8
Q
What are the 2 main protein degradation pathways in euks?
A
- Lysosome pathways
2. Proteasome pathways
9
Q
2 main post-translational modifications to signals during cell cycle
A
- phosphorylation (tyrosines, serines and threonines)
2. ubiquitination (lysines)
10
Q
What is the proteasome?
A
very large macromolecule of about 50 protein subunits that degrades many cellular proteins; hydrolyzes ATP to provide energy needed to degrade
11
Q
3 functions of protein degradation
A
- removes misfolded, damaged, or potentially toxic proteins
- controlled degradation of normal proteins provides appropriate levels to be maintained
- permits rapid responses to changing conditions
12
Q
What is ubiquitin?
A
highly conserved polypeptide of 76 a.a that marks proteins for degradation by proteasome
13
Q
How does a ubiquitin mark a protein for degradation?
A
Poly-ubiquitination- multiple ubiquitin molecules attach to a protein and are recognized by the proteasome
14
Q
What does a E3 Ub-ligase do?
A
achieves the specificity of the poly-ubiquitin
15
Q
4 ways that cyclin dependent kinase (CDK) activity is tightly regulated
A
- activation by cyclin-binding and t-loop phosphorylation by CDK Activating Kinase (CAK)
- Inhibitory phosphorylation of inhibitory of the active site by Wee1 Kinases (deactivates CDKs)
- Dephosphorylation of inhibitory sites by Cdc25 Phosphatases (activates CDKs)
- Physical Inhibition by CDK Inhibitors (CKIs)
16
Q
What does CDK Activating Kinase do?
A
phosphorylates a specific T loop which causes a shape change to the substrate which allows activation of the CDK
17
Q
What does Wee1 Kinase do?
Cdc25 Phosphatase?
A
Wee1 Kinase- phosphorylates and deactivates CDK activity
Cdc25 Phosphatase- dephosphorylates and activates CDK activity
18
Q
What do CDK Inhibitors do? (CKIs)
A
bind to CDK and cause a large rearrangement of CDK active sites making it inactive
19
Q
What are heterodimeric protein complexes?
A
consists of a regulatory subunit (cyclin) and a catalytic subunit (CDK) and controls the passage through cell cycle
20
Q
4 cyclin-CDK complexes and at which cycles they occur at
A
- Early G1: Cyclin D- CDK4,6
- Late G1/S: Cyclin E- CDK2
- S: Cyclin A- CDK2
- M: Cyclin A,B- CDK1
21
Q
cyclin and CDK conc throughout the cell cycle
A
CDK conc is constant, cyclin conc varies
22
Q
3 things that regulate the cell cycle
A
- cyclin/CDK complexes
- protein phosphates
- ubiquitin ligases
23
Q
G1 Cyclin-CDKs
A
activate transcription of a gene required at for DNA replication and assemble pre-replication complexes at origins
24
Q
SCF ubiquitin ligase
A
initiates passage through restriction point by polyubiquiting inhibitors of S-phase cyclin-CDKs so the inhibitors are degraded
25
S-phase cyclin-CDKs
activate DNA replication origins
26
Mitotic cyclin- CDKs
trigger entry into mitosis
27
Anaphase promoting complex (APC)
induces anaphase once kinetochores properly attached and triggers degradation of the cohesions that connect sister chromatids by enzyme seperase
28
4 examples of mitotic cyclin-CDKS at work
1. phosphorylate condensins which condenses chromosomes
2. phosphorylate nuclear lamines to breakdown nuclear envelope
3. phosphorylate MT-assc. proteins to change MT dynamics
4. phosphorylate ER or Golgi assc. proteins to reorganize the ER and Golgi
29
Definition of a cell cycle checkpoint
negative feedback mechanism that blocks cell cycle progression if wrong
inhibits cyclin-CDK transitions and allows time for correction or repair
30
2 main kinds of cell cycle checkpoints
1. DNA damage checkpoints
| 2. spindle checkpoints
31
3 components of cell cycle checkpoints
1. sensor proteins- detect abnormalities
2. transducer proteins- relay or amp damaged signal
3. effector proteins- halt cell cycle in response to damage signal
32
Cdc14 Phosphatase
activated when chromosomes are correctly segregated in anaphase
this phosphorylates and activates a protein that directs the APC to mitotic cyclins so they are broken down
changes cell to reshape into interphase form
33
3 ways we have studied the cell cycle
1. genetic studies in yeast
2. xenopus egg extracts
3. cellular studies in animals
34
what did genetic studies in yeast tell us about the cell cycle?
found cell division cycle (cdc) mutants and helped ID kinases and phosphorylates that control entry in mitosis
35
what did xenopus egg extract studies tell us about the cell cycle?
helped ID cyclin B as a component of maturation-promoting factor (MPF)
MPF activity low in interphase and high as entering mitosis
eggs arrested in G2 could be induced into M phase by MPF activity
36
Cyclin B
| normal vs. mutated
must be expressed then degraded for proper mitosis
in normal- mitosis
mutated- lacks a "destruction box" which normally promotes cyclin ubiquitination and degradation so it never breaks down and MTs don't depolymerize
37
Cyclin D
required for passage through G1/S restriction point
| is inhibited by microinjecting antibodies during Go or early G1, no DNA replication
38
Rec8
specialized cohesion unit and centromere
| allows proper segregation during anaphase I and II
39
Synapsis
pairing along lengths of chromosomes, happens in meiosis NOT mitosis
40
when do centromeres divide in mitosis? meiosis?
mitosis- anaphase
| meiosis- anaphase II
41
When does recombination happen in mitosis? meiosis?
mitosis- never
| meiosis- at least once
42
5 major tissue types
1. epithelial
2. connective
3. muscle
4. nervous
5. blood
43
2 ways cells have a connection
1. cell-cell adhesions (directly adhere) with cell adhesion molecules (CAMs)
2. cell-matrix adhesion (indirectly adhere) with binding of receptors to ECM
44
What is the extracellular matrix
complex meshwork or proteins and polysaccharides secreted by cells into extracellular spaces
holds tissues together and coordinates cellular functions by activating intracellular pathways
45
tight junctions
seals gaps between epithelial cells
46
adherens junctions
connects actin filaments bundle in one cell with that of next one
47
desmosomes
connects intermediate filaments in one cell to those of next
48
gap junctions
allows passage of small water-soluble molecules from cell to cell
49
hemi-desmosomes
anchors intermediate filaments of cell to ECM
50
focal adhesions
anchors actin filaments in cell to ECM
51
cis vs trans
cis- same side
| trans- opposite sides
52
cell adhesion molecules (CAMs)
can generate very tight adhesions when many weak interactions are combines
53
2 major families of CAMs and examples
1. hemophilic- same CAM both sides
ex: cadherins or Ig superfamily
2. heterophilic- different CAM classes
ex: intigrins or selectins
54
Cadherin works at 2 sites of cell adhesion
1. adherens junction- cadherins links directly to intracellular actin filaments via caterins
2. desmosomes- cadherins linked indirectly to intermediate filaments
55
2 actin filament anchoring junctions
1. adherens junction (cell-cell)
| 2. focal adhesions (cell-matrix)
56
2 intermediate filament anchoring junctions
1. desmosomes (cell-cell)
| 2. hemi-desmosomes (cell-matrix)
57
1 occluding junction
tight junction`
58
1 channel forming junction
gap junction
59
E-cadherin
main location in many epithelia with adherins junctions
60
tight junctions:
function
location
perform a barrier function and restrict diffusion of proteins b/t apical and basolateral regions and of macromolecules in spaces b/t cells
located between adjacent epithelial cells beneath apical surface
61
gap junction function
allow small molecules to pass directly between adjacent cells
gap where ions and molecules
62
3 kinds of ECM proteins (description and examples)
1. Proteoglycons (glycoproteins that cushion cells)
ex: perlecan
2. Collagens (insoluble proteins that provide structural integrity and mechanical strength
ex: sheet forming and fibriliar collagens
3. Multiadhesions matrix proteins (cross link receptors and other ECM components)
ex. laminin, fibronectin, nidogen/entactin
63
2 things that the ECM comprise
1. basal lamina
| 2. connective tissue
64
what is the basal lamina?
thin (260-120 nm) sheet of meshwork ECM components that underlies or surrounds many epithelial and non-epithelial tissues
links to cells by adhesion receptors
65
4 ubiquitous proteins found in the basal lamina and functions
1. Type IV collagen- trimetric protein that forms a fibrous 2D network
2. laminins- forms fibrous 2D network and binds to adhesion receptors
3. perlecan- crosslink networks
4. nidogen- crosslink networks
66
What is connective tissue in relation to ECM?
insoluble network of ECM that's rich in collagen
| volume is mostly ECM, not cells
67
examples of connective tissue
| most abundant cell and protein in connective tissue?
bone, tendon, and cartilage
fibroblasts
collagen
68
Structure of collagen
triple helix of 3 polypeptide alpha chains with high abundance of glycine, proline, and hydroxyproline
69
Protoglycans
subset of secreted or surface attacked glycoproteins that contain glycosaminoglycans (GAGs) and are involved in cell-matrix interactions
cushion cells
70
glycosaminoglycans
specialized polysaccharides chains which many (-) charges
| long linear polymers of repeating disaccharides
71
Hyaluronic acid
important GAG
| surrounds migrating and proliferating cells and produces lubricating quality in joints
72
fibronectin:
structure
function
long, flexible molecule with multiple domains for various bindings with collagens, proteoglycans, adhesion receptors, etc
important for organizing components of ECM, influence shape and movement of cells, organizes actin cytoskeleton, essential for migration and differentiation, bind to integrins on plasma membrane on plasma membrane
73
focal adhesions
contain integrin which mediates linkage between fibronectin in ECM and in intracellular actin cytoskeleton
74
loss of E-cadherin activity in cancer cells..
converts epithelial cells to malignant carcinoma cells
75
function of Integrins
adhesion receptor
provide a direct link between ECM and actin filaments through ABPs like talin and vinculin
controlled by signaling pathways
76
2 conformations of integrins
| why are there two?
1. inactive (low affinity)
2. active (high affinity)
reflects changes in cytoplasmic and ER domains of proteins
77
2 kinds of signaling mediated by integrins
1. inside-out: cytoskeleton can influence binding to ECM
| 2. outside-in: interactions with ECM can alter organization of cytoskeleton
78
how do integrins initiate signaling pathways
intigrins engaged by proteins in ECM signal to focal adhesion kinase and c-Src which activates P13K and Rho-family GTPases
signaling interacts with downstream
79
4 steps of cell motility
1. forward PROTRUSION of lamellipodium driven by force of actin polymerization
2. ADHESION of lamellipodia as it interacts with substrates in front of the cell
3. cell body TRANSLOCATION occurs via a dynamic network contraction model where myosin-mediated contraction of the actin at the junction between cell body and lamellipodia pulls cell body forward
4. De-adhesion and tail retraction as rear cell moves forward
80
3 enzymes that help drive motility
Rho, Rac, and Cdc42
81
role of Rho, Rac, and Cdc42 in cell motility
Cdc42 does adhesion at the front
Rac (front)- leads to Arp2.3 complex
Rho (back) leads to myosin II activation
82
normal function of:
Cdc42 and Rac
Rho
stimulates actin assembly and protrusion
| regulates focal adhesion formation and myosin-II mediated contraction
83
Arp 2/3 and Arpin
Arpin is Arp 2/3 inhibitor which is activated by same thing that activates the Arp 2/3 (Rac)
paradoxical circuit
84
6 steps of synaptic vesicle trafficking
1. import of neurotransmitter
2. movement of vesicle to active zone
3. vesicle docking at plasma membrane
4. exocytosis of neurotransmitter triggered by influx of Ca+2
5. reuptake of neurotransmitter
6. recovery of synaptic vesicles via endocytosis
85
3 classes of muscle
1. skeletal 2. smooth 3. cardiac
86
skeletal muscle broken down...
myofibers (muscle fibers) made up of multiple myobrils (contractile bundles) which are made up of sarcomeres (small contractile units)
87
2 filaments that make up the sarcomere
1. thin filaments (actin)
| 2. thick filaments (myosin II macromolecules)
88
Leiomodins
actin nucleators that are thought to create actin in muscle cells
89
CapZ and tropomodulin
CapZ- caps actin filament at (+) end, attaches filament to z-disk
Tropomodulin- caps (-) end of actin filaments
both stabilize a.f. by preventing polymerization and depolymerization
90
nebulin
protein that wraps along entire length of thin filament and acts like a ruler to control length of filaments
91
titin
huge fibrous protein that connects myosin ends to Zdisks, extends through filaments, and out on other side, keeps myosin centered
92
sliding model of contraction
sarcomeres shorten during contraction because myosin filaments slide past a.f.
bipolar myosin pulls a.f. and Zdisks toward it and causes sarcomere to shorten causing contraction
93
ATP and Ca+2 in skeletal muscle contraction
signal from motor neuron to muscle triggers an action potential in muscle cell that spread down t-tubule which extends into cytosol of myofibril; signal travels to sarcoplasmic reticulum which releases its stored Ca+2
94
When will myosin not bind to actin filament in muscle contraction
if Ca+2 not present
95
tropomyosin and troponin roles in muscle contraction
tropomyosin- forms a chain along thin filament and blocks myosin movement if no Ca+2 present
troponin- moves tropomyosin out of the way if Ca+2 is present
96
Immunological Synapses
focal point for exocytosis, endocytosis, and signaling at physical junction between lymphocytes
activation of tcell receptors and integrins leads to signaling that drives adhesion and cytoskeletal rearrangements of IS formation
97
5 steps of leukocytes crossing from blood to tissues
1. resting state
2. endothelial activation and leukocyte attachment and rolling (weak interaction b/t selectin receptors and carb ligands)
3. leukocyte activation (PAF activates integrin)
4. Firm adhesion via integrin/CAM bond
5. extravasation (leukocyte shape changes and migrates b/t epithelial cells in underlying tissues)
98
Cilia
Motile cilia
Flagella
```
tiny hairlike appendages with MT arrangement at core
function is to move fluid over cell surfaces
much longer, less numerous, on sperm and flagellates
```
99
axoneme
core of cilia and flagella
made up of 9+2 arrangement of MTs
9 outer doublets, 1 center doublet
arises from basal body
100
structure of axoneme
outer MTs connected to inner MTs via radical spokes
| inner MTs stabilized by inner sheath and connected by bridging protein
101
nexin
protein that connects out doublets of MTs and provides an elastic linkage between them to allow movement relative to one another
102
ciliary dynein
between a doublet of MT, on MT A and reach out and grabs MT B and mediates movement
103
function and structure of a basal body
function- nucleates cilia and flagella
| structure- 9 triplet MTs
104
structure of a centrosome
pair of centrioles surrounded by pericentriolar matrix (PCM)
105
primary cilium
present on almost every cell of the human body
originates from "mother centriole"
non-motile, acts as antenna to sense physical and biochemical signals in EC environment and transfer in
106
movement of motile cilia
asymmetric, power stroke followed by recovery stroke
107
movement of motile flagella
sinusoidal and symmetric
108
what provides the force for cilia of flagella beating
ATP dependent movement of ciliary dyein along MTs
109
Sliding MT hypothesis
ciliary and flagellar bending can be powered by sliding of outer doublet MTs relative to each other combines with nexin cross-links
sliding is powered by ATP-dependent ciliary dynein movement toward (-) ends of MTs
110
Intraflagellular Transport (IFT)
controls cilia biogenesis and signal transduction
111
totipotent
ability of single cell to divide and produce all the differentiated cells of organisms (only zygote)
112
pluripotent (and ex.)
ability to form all lineages of body (embryonic stem cells)
113
multipotent (and ex.)
ability of adult stem cells to form multiple cells of 1 lineage (hematopoetic stem cells- HSCs)
114
unipotent (and ex.)
cells form 1 type (spermatogonial stem cells)
115
3 defining properties of a stem cell
1. it is not itself terminally differentiated
2. it can divide without limit
3. when it divides, each daughter cell has two possible fates- can remain a stem cell or go through differentiation
116
what are the main roles of stem cells
to give rise to different cell types
| provide indefinite supply of fresh differentiated cells where lost, discarded, or in need of larger number
117
where are hematopoetic stem cells (HSCs) found?
in bone marrow, peripheral blood, and umbilical cord blood
118
2 kinds of transplantations assc. with stem cells. Explain.
1. bone marrow transplant (BMT)
2. peripheral blood stem cell transplant (PBSCT)
both restore stem cells that have been destroyed by chemo or radiation
commonly used in leukemia or lymphoma treatments
119
autologous vs, allogenic transplants
autologous- patients receive their own stem cells
| allogenic- receive stem cells from parent or sibling
120
what is the epidermis
forms outer covering of skins and creates a waterproof barrier that is self-repairing and continuously renewed
121
where are stem cells located
wherever there is a recurring need to replace differentiated cells that cant themselves divide
122
what is nuclear reprogramming
a switch in nuclear gene expression from one kind of somatic cell to that of an embryonic or other
123
3 reasons that nuclear reprogramming is of interest
1. if we ID reprogramming, we can better understand natural specialization and differentiation
2. enables us to analyze nature of diseases and screen for therapeutic drugs
3. cell-replacement therapy- defective cells replaced by normal cells of the same kind but derived from different cell type
124
transdifferentiation and plasticity
notion that somatic stem cells have broadened potency and can generate cells of other lineages (controversial in mammals)
125
2 major approaches for nuclear reprogramming
1. induced pluripotency
| 2. nuclear transfer to eggs
126
induced pluripotency
viral expression of 4 genes (Oct4, Sox2, Klf4, c-Myc) that can reprogram somatic cells to a state that is similar to embryonic stem cells (ES cells)
called induced pluripotent stem cells (iPS cells)
127
Induced pluripotent stem cells
somatic cells that are reprogramed to a state similar to ES cells after activation of Oct4, Sox2, Klf4, and c-Myc
128
events that could happen during reprogramming
changes in signal transduction pathways, chromatin reorganization and modification, actin rearrangements, methylation of DNA, miRNA expression, altered transcription patterns
129
nuclear transfer to eggs
somatic cell nucleus is transplanted to enucleated egg and in culture can give rise to ES cells
clones with surrogate mother
new cell types/organisms generated
130
examples of bacteria
coccus, coccobacillus, vibrio, bacillus, spirillum, spirochete
131
DNA virus ex
poxvirus, herpes, adenovirus, papilloma virus, parvovirus
132
RNA virus ex
influenza virus, mumps virus, rotavirus, rabies, HIV (AIDS virus), corona virus (common cold), poliovirus, LCM virus
133
are viruses alive?
not exactly alive, they require a living thing for replications
134
2 ways viruses can enter
| and what does it depend on
1. directly fusing with plasma membrane
2. via endocytic-based mechanisms (within endosomes or an non-enveloped capsules)
both depend of virus and cell type
135
cells vs microbial cells in human body
10^13 human cells, 10^14 microbial cells
136
normal flora
commensal microbes that are usual beneficial to the body
137
definition of pathogen
organisms that can cause overt disease in health people
| cause infectious disease
138
difference between pathogen and commensal microbe
pathogen can breech barriers and survive in places in the host that the commensal microbe can't
139
virulence factors
proteins that contribute to the ability of an organism to cause diseases when grouped together
140
genes of virulence factors
usually clustered together either in pathogenicity islands on bacterial chromosomes or on extra-chromosomal plasmids or carried on bacterial viruses
141
5 tasks a pathogen must perform to be considered successful
1. colonize their host (est. in specific location)
2. multiply (grow/divide in particular environment)
3. evade host responses- avoid or inactivate
4. cause damage- alter or disrupt normal host
5. spread- efficiently exit old host and go to new
142
4 common virulence factors
1. Toxins
2. adhesions and/or invasins
3. secretion systems
4. effectors
143
what are toxins
(virulence) proteins that are released from bacteria that alter or disrupt normal processes that occur either outside or inside the cell
144
adhesions and/or invasins
virulence proteins expressed on bacterial surface that promote attachment to cells or entry into cells
145
secretion systems
specialized molecular machines that translocate (inject) proteins from bacteria into host cells (Type 3 and Type 4) (T3SS and T4SS)
146
effectors
translocated proteins that alter or disrupt normal processes within host cell
147
AB Toxins
secreted by pathogens
has a A subunit- enzymatically active
B subunit- cell binding subunit
148
antharax lethal toxin
AB Toxin
| protease that modulates MAP kinase signaling cascades
149
Shiga Toxins (Stx)
AB Toxin
inactivates ribosome to prevent protein synthesis
bypasses late endocytic phase and goes from TGN to ER
150
Invasin protein
(mimics)
structural similarities to fibronectin,
surface protein that bacteria use to bid and enter host cell
ex: Yersinia
151
Internalins
multiple surface expressed proteins that bacteria bind to invade
ex: listeria monocytogenes
152
Intimin
surface expressed adhesion, doesn't recognize host cell
| used by EPEC and EHEC (strands of E.coli)
153
Type 3 Secretion System (T3SS)
can deliver effector proteins into cytosol of a host cell
| many bacteria use this to promote actin assembly and invasion
154
zipper and trigger mechanisms
actin-dependent
| bacteria use them to induce invasion into nonphagocytotic cells
155
3 strategies of bacterial cells once inside a host
1. vacuole escape
2. prevention of lysosomal maturation
3, growth with lysosomes
156
M.Tb compartment in host cell
remains in compartment with early endosomal markers and continues to communicate with plasma membrane via transport vesicles
157
Salmonella compartment in host cell
replicates in compartment with late endosomal markers and uses T3SS effector
158
Legionella compartment in host cell
replicate in compartment that is wrapped in several layers of ER membrane (uses T4SS effectors)
159
Chlamydia compartment in host cell
replicates in an exocytic compartment that fuses with vesicles forming from TGN (uses T3SS effector)
160
3 effectors that disrupt right junctions
1. pathogenic E. coli- uses T3SS effector proteins (EspF, EspG, and Map) to alter tight junction integrity
2. Salmonella- uses 4 T3SS (SipA, SopB, SopE, SopE2) to modify right junctions
3. Helicobacter pylori- translocates T4SS effector CagA to alter junctions
161
5 Steps of Litsteria invasion
1. attached to E-cadherin on cell surface of epithelial cells
2. induce own uptake by zipper mechanism
3. in phagosome, bacteria secretes protein Listerolysin (LLO)
4. in cytosol, bacteria replicates and continues to secrete LLO
5. LLO in cytosol rapidly degraded by proteasomes so host plasma membrane remains intact
162
what is listerolysin
a protein secreted by listeria bacteria as it enters the host cells
it forms oligomers in host cell membrane creating large pores and disrupting the membrance
163
ActA
protein on the surface of cells that stimulates actin assembly
activates Arp 2/3
structure is similar to WASP family proteins
164
pathogens and actin-based motility
many pathrogens use actin-based motility by using the force of actin polymerization to drive movement through cytoplasm
165
actin-based motility pathogens have virulence factors that work in 3 ways (examples)
1. nucleate actin (Rickettsia)
2. activate Arp2/3 Complex (Listeria and Baculorins)
3. activate N-Wasp (shigella, vaccinia, EPEC, EHEC)
166
3 Pathogen Controls of Actin Assembly
1. A36R and TIR activate tyrosine kinase signaling cascades that lead to actin assembly
2. ISSA and EspFu bind and activate N-WASP
3. Act A binds and activates Arp2/3 and Ca2 acts as formin mimic
167
EHEC 0157 characteristic
major foodborne pathogen assc. with undercooked ground beef of leafy veggies
-highly infectious, causes many illnesses in US, UK, Japan
hemolytic uremic syndrome (HUS) -kidney failure and death
168
carcinomas
sarcomas
leukemias and lymphocytes
cancers that arise from epithelial cells
arise from connective or muscle tissue
arise from blood cells
169
carcinogenesis
generation of cancer
170
2 heritable properties of cancer cells
1. reproduce in defiance of normal restraints on cell grown and division
2. invade and colonize territories normally conserved for other cells
171
tumor definition and the 2 options is can lead to
neoplasm- new growth
1. benign- noninvasive
2. malignant- ability to invade other cells by metastasis
172
most cancers derive from...
single abnormal cell with a mutation causing it to out-grow, out-divide, and out-live any of its neighbors
173
3 main genes when concerning cancer cells
1. proto-oncogenes
2. tumor suppressor genes
3. caretaker genes
174
normal function of proto-oncogenes
promote cell survival and proliferation
175
normal function of tumor suppressor genes
inhibit cell survival or proliferation
176
normal function of caretaker genes
repair or prevent DNA damage
177
5 kinds of tumor suppressor genes
1. proteins that regulate or inhibit cell cycle progression (ex. Rb)
2. receptors at signal transducers for hormones or development signals (ex. TGF-B)
3. checkpoint control proteins that arrest cell cycle if DNA damaged or chromosomes abnormal (ex. p53)
4. proteins that promote apoptosis
5. enzymes that function in DNA repair
178
Loss of function vs Gain of function
LOF- tumor suppressor and caretaker genes
| GOF- proto-oncogenes
179
Function of Rb
regulates G1/S phase
180
Un-phosphorylated Rb
binds to E2F transcription factor to prevent activation of many genes for DNA synthesis
181
What phosphorylates Rb
cyclinD-CDK4
182
phosphorylated Rb
releases E2F and activates transcription of genes needed for S phase
183
cancers in Rb from..
overproduction of cyclinD, loss of p16, loss of Rb
184
oncogenic transformation
cells that are rounder, less adherent to other cells, forms 3d clusters, and continue to grow which others have stopped
185
proto-oncogene definition
any gene that, if mutated, is capable of transforming cells in culture or induce cancers in animals
186
old school approach to studying proto-oncogenes
oncogene rasD was identified as it encodes activated form of Ras
rasD transforms some cultures of 3T3 cells
187
new school approach to studying proto-oncogenes
hybridizating methods using DNA microarrays can detect duplications or deletions of genes in tumor cells
fluorescently labeled DNA compared to normal
188
multi-hit model of cancer
many events are required for carcinogenesis
| overexpressed proto-oncogene and rasD
189
3 examples of proto-oncogenes and what oncogene they descended from
1. v-ras (from GTPase Ras)
2. v-myc (c-myc mutant)
3. v-src (c-src mutant)
190
how does p53 work
in response to hyperproliterative signals, DNA damage, hypoxia, and or telomere shoertening causes p53 levels to rise which causes cells to undergo cell cycle arrest, apoptosis, or replicative cell senescence
191
rise in p53 leads to..
cell cycle arrest, apoptosis, replicative cell cycle senescence
192
what is replicative cell senescence
cell looses ability to divide
193
loss of p53 function leads to
abolishing of cell cycle checkpoints
194
ATM-mediated phosphorylation of p53 leads to...
proper function of p53
195
active mam2 and p53 leads to...
mam2 bind to p53 and causes polyuquitation and degradation of p53
196
angiogenesis
growth of new blood cells
197
how to tumors persist and spread
cancer cells secrete molecules that stimulate angiogenesis, and malignant cancers invade nearby tissues and continuously proliferate and spread
198
cancer stem cells
can maintain many tumors, and can self renew to produce additional malignant stem cells and generate rapidly dividing amplifying cells
