NAME ___________________________________
BIOLOGY 052, SECTION 006
EXAM 2
SPRING 2008
+ PRINT YOUR NAME AT THE TOP OF EVERY PAGE.
+ USE A PEN, NOT PENCIL.
+ SIGN THE HONOR PLEDGE AT THE END OF THE EXAM.
+ USE ONLY THE SPACE PROVIDED FOR YOUR ANSWER.
+ QUESTIONS WILL BE GRADED ON BOTH HOW CORRECT AND HOW COMPLETE YOUR
ANSWER IS.
1. (20 points) Match the definition below with its term from the list above.
axoneme
cilium
filopodium
kinesin
tubulin heterodimer
neurofilament
keratin
filamin
flagellum
lamellipodium
myofibril
vimentin
desmin
Rho
contraction
catastrophin
pseudopodium
Rho protein family
Arp protein
dynein
dynamic instability
Listeria
myosin II
microtubule-associated protein
(a) A group of closely related monomeric GTPases that includes Cdc42, Rac, and Rho.
Rho protein family
(b) Bundle of microtubules that forms the core of a cilium or flagellum in a eukaryotic cell and is
responsible for their movements.
axoneme
(c) Long, highly organized bundle of actin, myosin, and other proteins in the cytoplasm of muscle cells
that contracts by a sliding-filament mechanism.
myofibril
(d) Flattened, two-dimensional protrusion of membrane, supported by a meshwork of actin filaments,
that is extended from the leading edge of crawling epithelial cells, fibroblasts, and some neurons.
lamellipodium
(e) Long, hairlike protrusion from the surface of a eukaryotic cell whose undulations drive the cell
through a fluid medium.
flagellum
f) Class of proteins that mediate the depolymerization of microtubules from their plus end.
catastrophin
(g) Intermediate filament protein that is predominantly expressed in epithelial tissue and gives
mechanical strength to skin.
keratin
(h) A protein that induces the nucleation of new actin filaments in the lamellipodia of motile cells.
Arp protein
(i) Microtubule-based motor that transport cargos to the minus ends.
Dynein
(j) Small G protein that activates cell contraction at the trailing edge of motile cells.
Rho
2. (10 points) One important role of Fas and Fas ligand is to mediate the elimination of tumor cells by
killer lymphocytes. In a study of 35 primary lung and colon tumors, half the tumors were found to have
amplified and overexpressed a gene for a secreted protein that binds to Fas ligand. How do you suppose
that overexpression of this protein might contribute to the survival of these tumor cells? Explain your
reasoning.
Overexpression of a Fas ligand would protect these cells from exogenously-induced apoptosis. (5
pts)
The secreted protein would prevent the Fas ligand from binding to Fas on the tumor cell surface,
thereby insulating them from the death-inducing interactions with killer lymphocytes. (5 pts)
3. (10 points) The drugs taxol, extracted from the bard of yew trees, and colchicine, an alkaloid from
autumn crocus, have opposite effects. Taxol binds tightly to microtubules and stabilizes them. When
added to cells, it causes much of the free tubulin to assemble into microtubules. In contrast, colchicine
prevents microtubule formation. Taxol and colchicine are equally toxic to dividing cells, and both are
used as anticancer drugs. Based on your knowledge of microtubule dynamics, explain why these drugs
are toxic to dividing cells despite their opposite modes of action.
As cells enter mitosis, cells reorganize their microtubules to build a spindle from the interphase
microtubule array and this requires dynamic instability. (5 points) Inhibition of dynamic
instability will also interfere with microtubule capture by kinetochores, thus setting off the mitotic
checkpoint and leading to apoptosis. (5 points)
4. 10 points) Filamin is an actin-binding protein that cross-links actin filaments at roughly right-angles
to produce a viscous gel that is required for cells to extend sheet-like lamellipodia. Why is the loss of
filamin in melanoma cells bad news for the melanoma cells, but good news for the patient?
Lamellipodia mediate protrusion of the leading edge - without it cellular migration is inhibited (5
points) This inhibition of migration decreases the likelihood of metastasis, and improves the
prognosis for cancer patients (5 pts).
5. (20 points) Match the definition below with its term from the list above.
adaptation
adaptor
protein kinase A
endocrine cell
mitogen
scaffold protein
neurotransmitter
nitric oxide (NO)
signaling cascade
steroid hormone
hormone
intracellular signaling protein
ion-channel-coupled receptor
contact-dependent signaling
monomeric GTPase
enzyme-coupled receptor
negative feedback loop
second messenger
serine/threonine kinase
nuclear receptor superfamily
phosphorylation
phospholipase C
positive feedback loop
MAP kinase cascade
protein kinase C
protein phosphatase
receptor
paracrine signaling
GPCR
NO synthase (NOS)
GTP-binding protein
tyrosine kinase
adenylyl cyclase
(a) Enzyme that cleaves inositol phospholipids into diacylglycerol (DAG) and inositol triphosphate
(IP3).
Phospholipase C
(b) Short-range cell-cell communication via secreted local mediators that act on adjacent cells.
paracrine signaling
(c) A signal relay chain involving multiple protein kinases, each of which is activated by
phosphorylation and then phosphorylates the next protein kinase in the sequence.
MAP kinase cascade
(d) Hydrophobic signaling molecule with a characteristic four-ringed structure derived from cholesterol.
steroid hormone
(e) Class of small molecule that is formed in the cytosol, or released into it, in response to an
extracellular signal that helps to relay the signal to the interior of the cell.
Second messenger
(f) Specialized animal cell that secretes a hormone into the bloodstream.
Endocrine cell
(g) Enzyme that transfers the terminal phosphate group of ATP to a specific amino acid of a target
protein.
kinase
(h) Cell-cell communication in which the signal molecule remains bound to the signaling cell and only
influences cells that physically touch it.
Contact-dependent signaling
(i) Small signal molecule secreted by the presynaptic nerve cell at a chemical synapse to relay the signal
to the postsynaptic cell.
neurotransmitter
(j) Enzyme that catalyzes the conversion of ATP into cAMP.
Adenylyl cyclase
6. (10 points) A single amino acid change in Ras eliminates its ability to hydrolyze GTP. Roughly 30%
of human cancers have this mutation in Ras. You have just identified a small molecule inhibitor that
prevents dimerization of a receptor tyrosine kinase that signals via Ras. Would you expect this small
molecule inhibitor to be useful as a drug to treat cancers that that express this common, mutant form of
Ras? Why or why not?
The small molecule would not be effective in treating cancers with mutationally activated Ras
proteins. (5 points) Activated Ras causes problems because it signals independently of upstream
activation. Preventing receptors from dimerizing would have no effect on the activity of mutant
Ras. (5 pts)
7. (10 points) Match the definition below with its term from the list above.
anaphase-promoting complex (APC)
M-cyclin
cyclin-dependent kinase (Cdk)
cyclin-Cdk complex
executioner caspase
procaspase
checkpoint
mitotic checkpoint
retinoblastoma protein
Bcl2
M-Cdk
S-cyclin
ubiquitin
cytochrome c
survival factor
(a) Protein that is synthesized and degraded over the course of the cell cycle and drives cells into
mitosis.
M-cyclin
(b) A member of the family of protein kinases that have to be complexed with a cyclin protein in order
to become active.
Cyclin-dependent kinase (Cdk)
(c) The inactive form of the class of proteases that mediate apoptosis.
procaspase
(d) The ubiquitin ligase that promotes the destruction of a specific set of proteins, thereby promoting the
separation of sister chromatids and the completion of M phase.
Anaphase-promoting complex (APC)
(e) Mitochondrial protein that triggers the endogenous apoptotic pathway.
Cytochrome c
8. (10 points) Antibodies are Y-shaped molecules that carry two identical binding sites. Imagine that
you have obtained an antibody that is specific for the extracellular domain of a receptor tyrosine kinase.
If cells were exposed to the antibody, would you expect the receptor tyrosine kinase to be activated,
inactivated, or unaffected? Explain your reasoning.
The antibody is likely to activate the receptor tyrosine kinase (3 points). RTKs are activated when
they are dimerized and their catalytic cytoplasmic domains are brought together (4 points). Thus,
an antibody with two identical binding sites would artificially dimerize receptor and activate them
(3 points).
9. (10 points) Match the definition below with its term from the list above.
kinetochore
kinetochore microtubule
interpolar microtubule
contractile ring
chiasma
mitosis
meiosis
anaphase A
cytokinesis
mitotic chromosome
haploid
dynein
condensin
cohesin
anaphase B
centrosome
separase
metaphase plate
(a) Stage of mitosis in which the spindle poles move apart.
Anaphase B
(b) Microtubules that overlap in the spindle midzone and interact via their plus ends, generating an
antiparallel array.
Interpolar microtubules
(c) Centrally located organelle of animal cells that, after duplication, organizes each spindle pole during
mitosis.
centrosome
(d) Protease whose activation at the end of metaphase results in the cleavage of cohesin and the
separation of sister chromatids.
separase
(e) Specialized region of the mitotic chromosome that acts as the primary attachment point with
microtubules.
kinetochore
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ASSIGNMENT.
SIGNED _____________________________________