Exam 2 Flashcards
what are immediate early genes
react right away to GF
What are delayed early genes
Occurs with a lag
What do tyrosine phosphorylations do
control location of cytoplasmic signaling proteins and therefore their actions
Use the structure of Src to explain tyrosine phosphrylation
SH1- interacts with substrate to cause enzymatic reaction
SH2- docking site for protein signal pathway
SH3- stabalize binding site
What are the three major pathways of RAS
Ras-RAf
PI3K
Ral-GEF
What is the RAS-Raf pathway
map kinases pathway
results in chromatin remodeling, proteing synthesis or transcription
What is the PI3K pathway
Stimulates Akt/PKB
inhibits apoptosis, stimulates protein synthesis, stimulates cell proliferation, progression of cell cycle
What is the Ral-GEF pathway
causes alteration sin cytoskeleton that allow cell to divide and affect cell mobility
Explain an example of direct signaling
Jak-STAT pathway- activation of Jak leads to STAT dimerization and migration to nucleus
What is direct signaling
receptor migrates directly to nucleus
not cascade like
What are integrins
interact with cytoskeleton
What is integrin signaling
transmit signaling through focal adhesion kinase proteins
What types of pathways does integrin signaling activate
pathways to decline likelihood of apoptosis
What triggers anoikis
lack of binding to ECM
what is anoikis
a form of apoptosis that activates caspase-3
Describe the Wnt-Beta-Catenin pathway
If wnt is bound, B-catenin evades degradation and goes to the nucleus and turns on proliferation expression by binding to Tcf/Lef
Explain the G-protein coupled Receptors pathway
B-arrestin activates kinases for cell proliferation and survival
alpha activates Raf/Ras, gamma and beta activate PI3K, Raf/Ras, src
explain the nuclear factor KB pathway
bound to inhibitor
when phosphorylated, inhibitor is degraded and moves to nucleus to activate cell growth and division
Explain the notch pathway
interaction with ligand cleaves off fragment of notch and goes to necleus for cell proliferation
NF-KB pathway can cause what cancers
breast, lymphomas, myelomas
Notch pathway can cause what cancers
cervical, colon, prostate, and lung
Explain the patched-smooth pathway
when smooth is activated, allows Gli into the nucleus uncleaved to promote transcription
Patched-smooth pathway can cause what cancers
basal cell carcinoma, glioblastomas
what are dual address pathways
something exists in the cytoplasm and gets moved to the nucleus to become transcription factors
what are the types of dual adress pathways
Jak-STAT Wnt-B-catenin Nf-KB Notch Patch-smooth TGF-B
Explain the TGF-B pathway
Smad heterotrimeric complex goes to nucleus to associate with transcription factors
TGF-B pathway is associated with what cancers
almost all carcinomas
Examples of negative feedback loops to regulate signal pathways
Ras binding to GTP causes sprouty to inhibit SH2 and Raf
Ras bound to Gap stops Ras
Gli moving to nucleus makes more patched and inhibits smooth
Examples of positive feedback loops to regulate signal pathways
activation of PKC degrades NF1 which allows RAs to become active
Ways to cause cancer through pathways
alter intrinsic activity of signaling molecules
alter concentration of signaling molecules
alter localization of signaling molecules
what occurs at the G1 check point
look for DNA damage
what occurs at the S phase checkpoint
make sure DNA only replicated once
what occurs at the G2 checkpoint
is DNA replication complete
what occurs at the mitosis checkpoint
are chromatids properly assembled
What happens at the R-point
the cell no longer responds to mitogenic GFs and TGF-B
what is cyclin D controlled by
macrphages, pathways
why are there three types of Cyclin D
different version induced by different pathways
inhibitors of Cyclin/CDKs
TGF-B, Akt/PKB, p21, p27
What are the three pRBs and what are their functions
p130 imposes Go quiescence
pRB regulates progression through G1
p107 regulates late G1/S
what does hyperphosphorylation of pRB do
discourages transcription
What do E2F/pRB complexes do
modify chromatin conformation and discourage transcription
explain the pRB pathway
mitogen - receptor Ras- cyclins and e-pRB inactivation or E2F activation - S phase
how does Myc affect pRB
increases transcription of proteins that inactivate pRB
increases transcription of E2F family genes
increases transcription of proliferation inhibitors
Role of Cyclin D
interacts wiht estrogen receptor and TFs to control gene expression
Role of Cyclin E
may help regulate centrosom duplication
Examples of dominant mutations
ras, myc point mutations, receptor mutations that cause constant signaling, proto-oncogenes
examples of recessive mutations
tend to be tumor supressos genes
retinoblastoma tumor supress gene example
dominant phennotype, recessive genotype
needs to lose both copies for cancer development
what are ways LOH can occur
mitotic recombination gene conversion during DNA repair deletion nondisjunction translocations
how do we detect LOH
RFLPs track loss of paternal or maternal allel
PCR
overlapping deletions
How can you inactivate a tumor suppressor
methylation of CpG in promoter
What are the major tumor suppressor genes
Rb and p53
Why is p53 mutated easily
because needs all 4 copies to work properly
what does p53 control
apoptosis, DNa repair, blocking of angiogenesis and cell cycle arrest
What are the four hallmarks of apoptosis
Membrane blebbling
Pyknosis
DNA fragmentation
Formation of apoptotic bodies
Ways to detect apoptosis
Phosphatidylserine on membrane
Tunel assay
Antibody to activate cascade 3
What causes intrinsic apoptosis
DNA damage, low o2 , uv damage
Explain intrinsic apoptosis
Cytochrome C with apaf1 plus procaspase makes the wheel of death
What causes extrinsic apoptosis
Death receptors and death ligands
Explain extrinsic apoptosis
Form timers that activate FADD
Procaspase cleaved to caspase turns into executioner procaspases
Then extrinsic and intrinsic come together
What proteins open and close the cytochrome C channels
Bcl2 keeps channels closed
Bax/bak open channels up
what is the hayflick limit
the amount of times a cell can divide
what are reasons cells stop dividing
accumulated oxidative damage
cell counts its division amounts
when does a cell enter crisis
when the cell goes past the Hayflisk limit
when less than 3,000 base pairs
What happens in crisis
BFB cycles build then the telomeres snap whereever
How does cancer save telomeres
telomerase
ALT
how do cells escape crisis
expression of telomerase
Why are mice good models for telomeres
have longer telomeres
How do BFB cycles contribute to cancer
genetic instability
inactivates p53
