Learning Objectives Flashcards
1
Q
properties of malignant cancer cells
A
- unresponsive to normal signs of proliferation control
- de-differentiated
- invasive
- metastatic
- clonal origin (came from one cell)
- lack contact inhibition
- more glucose transport
- immortal
2
Q
steps for carcinogenesis
A
- normal cell
- increased proliferation
- neoplasia
- carcinoma
- metastasis
3
Q
cytogenetic abnormalities associated with malignancy
A
- chromosome translocation, deletion
- bringing a promoter near an oncogene
- interrupting transcription
4
Q
retinoblastoma gene is on chromosome _____
A
13q14
5
Q
retinoblastoma gene loss can be detected by ________________
A
PCR, Southern blot
6
Q
RB is a ___________ gene
A
tumor-suppressor
7
Q
APC encodes for a protein that regulates localization of ___________ protein
A
beta-catenin
8
Q
When APC is lost, beta-catenin ________________
A
goes to nucleus to produce transcription of oncogenes
9
Q
p53 is (homozygous/heterozygous) but a ___________________
A
heterozygous, tumor suppressor
10
Q
adenovirus E18, HPV E6, etc. have __________ that inactivate _____
A
oncogenes, p53
11
Q
v-src
A
phosphorylates tyrosine residues in other proteins
12
Q
v-erb
A
mimics epidermal growth factor receptor
13
Q
v-sis
A
mimics platelet-derived growth factor
14
Q
Li-Fraumeni criteria
A
- proband with sarcoma diagnosed before age 45
- first degree relative with any cancer before age 45
- first or second degree relative with any cancer before age 45 or a sarcoma at any age
15
Q
clinical manifestations of Von Hippel-Lindau (VHL) disease
A
- hemangioblastoma (CNS, retina)
- clear cell renal cell carcinoma
- bilateral kidney cysts
- pheochromocytoma
- pancreatic cysts and pancreatic neuroendocrine tumors
- endolymphatic sac tumor
- cystadenomas of genitourinary tract
(BE HPPCC)
16
Q
VHL is a _________ gene located on chromosome ___
A
tumor-suppressor, 3p25-26
17
Q
VHL targets ______ for ubiquination and degradation
A
HIF
18
Q
phospholipid
A
glycerol-3-phosphate backbone with two fatty acyl chains (saturated or mono- or poly-unsaturated) at one end and polar head group at other
19
Q
sphingolipid
A
- long acyl unit (sphingosine) with either of two polar head groups and an attached fatty acid chain
- NH instead of one of the C’s
20
Q
cholesterol
A
hydroxylated ring at one end and fatty acid chain on other
21
Q
Uptake and synthesis of cholesterol are regulated by ________
A
SREBP
22
Q
With low cholesterol, the transcription factor is released from SREBP via ______________________
A
RIP (regulated intramembrane proteolysis)
23
Q
Proteases that cleave SREBP release ___________
A
basic helix-loop-helix
24
Q
_______ binds SREBP and sterols like cholesterol
A
SCAP
25
_______ binds SCAP when cholesterol is high
Insig
26
plasma volume
3 liters
27
ECF volume
13 liters + 5 for "third space"
28
ICF volume
27 liters
29
physical forces that can determine the gating properties of ion channels
- electric field (voltage-gated, membrane potential)
- mechanical (stretch)
- chemical (synaptic receptors)
- temperature
30
mechanisms cells evolved to keep from swelling and bursting
- make cell membrane impermeable to water
- build wall around cell which resists osmotic pressure
- balance water concentrations osmotically
31
molarity
number of moles of solute/L of solution
| -measure of concentration
32
osmolarity
total concentration of solute molecules (sum of molarity)
33
equivalents
number of "combining weights" of an ion per liter
| -convert mosM for each ion, multiply most by valence of each ion
34
tonicity
effect of a solution on a cell
35
_____ protein regulates dissociation of SNARE protein
NSF
36
arterial blood pH
7.34-7.44
37
venous blood pH
7.28-7.42
38
concentration of HCO3- in blood
24mmHg
39
PCO2 in blood
40mmHg
40
One clinical exam finding that suggests irritable bowel disease is _________
erythema nodosum
41
major metabolic disturbances in DKA
- hyperglycemia (elevated blood sugar)
- acidosis
- potassium derangement
- dehydration
42
action of insulin in liver
- stores glucose (as glycogen) and lipid
| - stops lipid and glycogen breakdown
43
action of insulin in muscle
- stores glucose
| - makes protein
44
action of insulin in adipose
-stores glucose and triglyceride
45
loss of RB gene can occur via...
- local events
- somatic recombination
- chromosome loss
- loss and duplication
46
In FAP, the mutation is a change from ________ to __________
glutamic acid to glutamine
47
BRCA1 is important in regulating _____________
quality control for DNA damage
48
Most mutations in p53 are _________ mutations
missense
49
Li-Fraumini syndrome is inherited in an ________ fashion
autosomal dominant
50
common ways cancer-associated "hits" can occur
- point mutation (activating oncogene or suppressing tumor inactivation)
- amplification
- deletion
- epigenetic silencing via methylation
- insertion of retrovirus containing an oncogene
51
T/F: In Li-Fraumini syndrome, "hits" can be on different genes
true
52
VHL comes from a ________ mutation in ______ of the VHL gene
missense, exon 3
53
VHL is an ___________ inherited cancer syndrome
autosomal dominant
54
VHL is a ___________ gene
tumor-suppressor
55
Where are CNS hemangioblastomas found in patients with VHL?
cerebellum, brainstem base, cervical spine (not forebrain)
56
actions of VHL protein
- regulates HIF (hypoxia inducible transcription factor)
- suppresses aneuploidy
- microtubule stabilization/primary cilia maintenance
57
Gag encodes for ________
internal virion proteins
58
Env encodes for ______________
membrane glycoproteins
59
Pol encodes for ______________
reverse polymerase
60
V-myc mimics ________________
c-myc proto-oncogene (cell growth/division)
61
_____________ are the most common cause of death in patients with Von Hippel Lindeau
renal cell carcinomas
62
Describe the position of activation and inactivation gates in action potentials
- rest: activation closed, inactivation open
- rising: both open
- falling: activation open, inactivation closed
- hyperpolarization: both closed
63
causes of hyperkalemia (2)
- K+ escaping from cells
| - kidney that can't keep [K+]o below 5mM
64
systemic therapies for metastatic renal cell carcinoma include...
- vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors
- MTOR inhibitors
- immunotherapies
65
Gating of ion channels is controlled by... (3)
- temperature (hot/cold)
- mechanical deformation
- membrane potential
- extracellular chemicals (taste, olfaction, neurotransmitters)
- intracellular second messengers (ATM, cAMP, Ca2+)
66
major functions of the ER
- synthesis of lipids
- control of cholesterol homeostasis
- synthesis of proteins on membrane bound ribosomes
- co-translational folding of proteins and early post-translational modifications
- quality control
67
major functions of golgi
- synthesis of sphingolipids
- post-translational modification
- proteolytic processing
- sorting proteins and lipids for post-golgi compartments
68
pentameric ligand gated channels
- cys-loop family
| - each subunit has four transmembrane alpha helices
69
ionotropic glutamate receptors (NDMA)
two of the four subunits bind glutamate and other two bind glycine
70
chloride channels
- gates open and close independently of each other
- H+-Cl- exchangers
- CLC chloride channels stabilize resting membrane potential
71
factors that affect channel selectivity
- charge (ionic valence too)
- size
- dehydration
- number of binding sites
- gating of Kv and Nav channels
72
p53 is a ______________________
transcription factor
73
p53 regulates ___________ and _________________
microRNA, protein-coding genes
74
reflection coefficient
how well the membrane reflects the substance (0 = water, 1 = impermeable)
75
equilibrium potential of RBC
-5
76
equilibrium potential of WBC
-30
77
equilibrium potential of neuron
-70
78
equilibrium potential of muscle
-80
79
equilibrium potential of glial cells
-90
80
barrier nucleoporins contain ____________ repeats
phenylalanine-glycine
81
What are karyopherins?
importins/exportins (interact directly or indirectly with cargo and FG nups)
82
Ran.GTP
- high levels in nucleus, helps transport cargo out of nucleus
- gets hydrolyzed (GTP --> GDP) in cytoplasm to release cargo
83
NFT2
- brings cargo and Ran.GDP from cytoplasm to nucleus
| - GDP --> GTP
84
Brownian Ratchet
ATP-dependent helicase that unravels nascent RNA to allow binding, dragging nascent mRNA through nuclear pore complex (RNA movement is slower than regular protein)
85
methods of regulating cargo binding to importing/exportins
- intramolecular masking
- intermolecular masking
- affinity enhancement
86
N-linked glycosylation amino acid series
Asn-X-Ser/Thr (X = any AA except proline)
87
post-translational modifications that occur in the golgi
- glycosylation (sugar and sulfates being put on)
| - sorting
88
______ is a sequence of amino acids that targets that amino acid to be recycled back to the ER
KDEL
89
The cholera toxin is produced by a ________________
bacteriophage
90
The cholera toxin binds to a ___________ via _____
ganglioside GM1, cAMP
91
Dukoral cholera vaccine
killed 01 x2 and CtxB strains
92
Shanchol cholera vaccine
killed 01 and 0139 strains
93
3 major virulence factors of cholera
- cholera toxin (CT)
- o-specific polysaccharides (OPS)
- pili: support colonization (TCP)
94
ERp57 provides ER quality control by...
allowing formation of disulfide bonds for proper folding of enzymes
95
_____________ are folding sensors in the ER
UDP-glucose: glycoprotein glucosyltransferases (UGGT)
96
Proteasomes only degrade...
poly-ubiquinated proteins
97
Lysosomes degrade ____________ targeted via the ____________
all cellular components, endocytic pathway
98
Functions of macroautophagy
- survival and stress conditions
- recycle mitochondria
- antigen presentation
- neuroprotection
- removes intracellular pathogens
- aging
- tumor suppression (if you don't have it) and promotion (if you already have it)
99
____ has only an activation gate whereas ____ has both activation and inactivation gates
Kv, Nav
100
At the beginning of the relative refractory period, most K+ gates are...
open
101
Myelin ________ capacitance and _________ resistance
decreases, increases
102
What is the strongest force in nature?
strong nuclear force
103
Each 10-fold increase in concentration gradient is equivalent to a force of ____mV
60mV
104
Ways to diagnose hyperkalemia (2)
- EKG
| - K+ levels
105
If an ion is at equal concentrations across a membrane, what is its equilibrium potential?
0
106
Functions of BRCA1 and BRCA2
- regulation of S-phase checkpoint
- regulation of G2/M phase checkpoint
- homologous recombination
107
Herceptin is...
a synthetic antibody that attacks HER2/ERBB2 receptors
108
Order smallest to largest surface area: cytoskeleton, internal membrane, plasma membrane
plasma membrane, internal membrane, cytoskeleton
109
The apical membrane is (positive/negative) compared to basolateral
negative
110
The major cellular defect in cholera is overproduction of ______
cAMP
111
SRPs have an abundance of ___________ at their signal sequence binding pockets
methionine
112
Cholera is caused by _________ diarrhea
secretory
113
The __-subunit of proteasome cleaves after __________
beta, acidic amino acids
114
T/F: Caveolae form without coat proteins
true
115
Caveolin-3 is expressed in _________ and ___________ muscle
skeletal, cardiac
116
______ competes with caspase-8 for binding to FADD and prevents apoptosis
FLIP
117
Most cases of Li Fraumini are (inherited/sporadic). Most cases of Von Hippel-Lindau are (inherited/sporadic).
inherited(?), inherited (80%)
118
Lipid bilayer components are synthesized in the _____
ER
119
Features of Nav and Kv that lead to sidedness
- selectivity filter near extracellular side
- vestibule near intracellular side
- activation/inactivation gates near intracellular side
120
Direction of conductance (is/is not) unidirectional. Direction an action potential travels (is/is not) unidirectional
is not, is
121
In chaperone-mediated autophagy, proteins are ultimately delivered to the ______________
lysosome
122
Autophagy production protects against __________ toxicity
polyglutamine
123
When caspases are activated, _______ gets cleaved via Bcl-2 and Bcl-xl binding to BH3 domains so autophagy can't occur
beclin protein
124
Nucleoporin misregulation is associated with...
- cancer
- aging
- oxidative damage
125
3 mechanisms of protein transport
- vesicular
- gated
- transmembrane
126
In DKA, you have a net K+ ______________
depletion
127
driving force
at any instant, the difference between Vm and Eion
128
heat map
gene copy number is correlated with tumor grade
129
proteasomes are located in the ________ and _______
cytosol, nucleus
130
In _____ channels, each domain is a polypeptide
Kv
131
In Nav channels, ___ polypeptide(s) comprise(s) entire channel
one
132
ionotropic
neurotransmitter is directly coupled to channel
133
metabotropic
2nd messenger pathway that affects physically separated ion channels
134
________ protein regulates G-actin concentration and ADP to ATP exchange
profilin
135
________ is an actin-capping protein
gelsolin
136
_______ is important for depolymerizing/severing
ADF/cofilin
137
mechanisms for signal termination
- uptake, breakdown, diffusion
- desensitization of receptor
- termination initiated by another signal
- termination-dedicated enzymes
- feedback inhibition
138
During the refractory period of an AP, the activation gates are ________ and inactivation gates are ___________
open, shut
139
Under hypoxic conditions, accumulation of HIF activates VEGF transcription, which leads to ________________
- angiogenesis (blood vessel formation)
- metabolism
- apoptosis
- cancer growth and survival
140
Protein kinases can be classified based on... (4)
- residues they phosphorylate
- activating stimulus
- substrate protein
- phylogenic relationships
141
______ causes nsec1 to release syntaxin (leading to zippering)
calcium
142
metabolic acidosis vs. alkalosis
acidosis: too low bicarb
alkalosis: too high bicarb
143
respiratory acidosis vs. alkalosis
acidosis: too high Pco2
alkalosis: too low Pco2
144
S5 and S6 helices of ion channels form...
the ion conducting pathway and selectivity filter
145
The strongest association allele for MS is _______
HLA-DRB1
146
The contribution of genes on MS is likely driven by ______________ and _____________
gene-gene interactions, HLA effect on immune responses
147
pentamer ligand-gated channels
- heteropentamers
- 4 transmembrane alpha helicies per subunit
- M2's surround central ion-conducting pathway
- selective for Cl- or cations
148
tetrameric ligand-gated channels
- 4 subunits with 3 alpha helices per subunit
- NDMA: 2 glutamate, 2 glycine
- ionotropic glutamate receptors
149
CLC chloride channels
- dimers
| - some are H+/Cl- exchangers
150
aquaporins
- tetramer
- water pore and gated, central ion pore
- excludes all ions (including H+)
151
__________ cleaves the proteins in the proteasomes
Beta subunit
B1 = acidic aa
B2 = basic aa
B5 = chymotrypsin-like
152
______ genes are required for formation of an autophagosome
Atg
153
The ____ subunit of a microtubule is the + end and the ___ subunit of a microtubule is the - end
beta, alpha
154
A _________ stabilizes the ends of microtubules
GTP cap
155
Functions of microtubules
- cellular cytoskeleton
- cilia
- cell division
- intracellular transport
156
Intermediate filaments are composed of _____________ that can form __________
8 tetramers, coiled coils
157
Predominant proteins found in...
- microtubules
- intermediate filaments
- microfilaments
- microtubules: tubulin
- intermediate filaments: vimentin, keratin, neurofilament protein, etc.
- microfilaments: actin
158
GTP favors _________ growth while ATP favors __________ growth
microtubule, microfilament
159
Steps of actin filament formation (2)
- nucleation
| - extension (from + end)/retraction
160
Actin filament structure is regulated by... (4)
- G-actin polymerization (profilin)
- ADP to ATP transition (profilin)
- capping (gelsolin)
- depolymerization/severing (ADF/cofilin)
161
Functions of actin (4)
- epithelial cell polarity
- contraction
- cell motility
- cell division
162
Two classes of signaling molecules and examples of each
- lipophilic (hydrophobic): steroids
| - hydrophilic (lipophobic): peptides, proteins, amino acids
163
_____ is a signal terminator that breaks down cGMP to GMP
PDE5
164
Cooperation enables regulation of enzyme activity over a (wider/narrower) range of substrate concentrations
narrower
165
Pertussis locks the G-protein in the __________ state
inactive
166
Cholera locks the G-protein in the _________ state
active
