Dr. White-Genes (when things go right and wrong) Flashcards
What is signal transduction?
cell to cell communication
what happens if the lectin gene is knocked out? (mice used as example) What is this an example of?
if leptin is knocked out, the mouse will not think that it is full and will continue eating, resulting in a fat mouse. This is an example of signal transduction.
Describe endocrine signaling
long distance signaling, signal goes from bloodstream to distant target cells.
Freely diffusible signal and long lasting
Describe paracrine signaling
acts locally and affects nearby cells (not as freely diffusible)
short lived signal
Describe synaptic signaling
acts locally and affects cells nearby (not as freely diffusible)
short lived signal
ex: neurotransmitters
Describe autocrine signaling
- cells respond to signals that they themselves release to cells of the same type
- cell secretes signal that feeds back and binds to a receptor on its own surface
ex: growth factor in cancer cells
Describe direct cell signaling
Ag-presenting cells to T cells
ex: immune cells
What does the extracellular domain of the G protein coupled receptor do?
binds to ligand
What does the transmembrane domain of the G protein coupled receptor do?
anchors receptor
What does the cytoplasmic domain of the G protein coupled receptor do?
associates with G protein
G proteins are ______ proteins composed of how many subunits?
heterotrimeric, 3 subunits: alpha, beta, gamma
What do the heterotrimeric G proteins do?
regulate target enzymes
REVIEW THE PATHWAY OF G PROTEIN SIGNALING
slide 13 of lecture
What does adenylyl cyclase do?
generates cAMP which then goes on to interact with it’’s target protein to cause a biological response
What occurs in cholera?
Cholera toxin modifies G protein by keeping the G alpha protein in the GTP active form indefinitely, making the pathway always active. Cl- and water pump out of cell in intestine, causing severe diarrhea.
cAMP interacts with target proteins to cause what?
a biological response
cAMP activate ______ which has ____ subunits
cAMP dependent protein kinase (PKA), 4 subunits
When 2 cAMP molecules bind to the regulatory subunits of PKA what happens?
release of active C subunits
Describe receptor tyrosine kinases (RTKs)
play important role in signal transduction
enzyme linked receptor
used for response to growth factors
What are the components of RTKs?
extracellular domain
transmembrane domain
cytoplasmic domain which transmits signal through tyrosine kinase domain and adds phosphates to tyrosine on proteins
review signaling by protein phosphorylation
slide 21
What happens when a ligand binds to the RTK?
causes conformational change which induces dimerization of two receptor monomers and autophosphorylation occurs
Autophosphorlyation of the the RTK causes what?
the receptor to act as a scaffold or docking sites to recruit other proteins to the plasma membrane, outside event (binding to receptor) gets transacted to a response inside the cell
review RTK cascade
slides 24-27
review JAK-STAT process
slide 28
review serine-threonine receptor and smad
slides 29-30
when signal is not turned off, Ras is constitutively activated from a point mutation of Gly to ____ and results in what?
Val, resulting in mutation (frequently found in human cancer)
What makes cells different?
differences in gene expression
describe the helix turn helix DNA-binding domain structural motif
- simplest
- two alpha helices connected by short chain of amino acids that make turn at fixed angle
- longer helix portion= recognition module-DNA binding module
- binds DNA as dimers
describe the zinc finger domain
- DNA binding motif includes Zn atom
- binds to major groove of DNA
Describe the leucine zipper motif
- two alpha helical DNA binding domain
- dimerizes through leucine zipper region
- interactions between hydrophobic amino acid side chains (Leu) at every 7 aa down one side of alpha helix to form zipper structure
- grabs DNA like clothespin
describe the helix loop helix domain
- consists of a short alpha chain connected by a loop to a second longer alpha chain
- can occur as homodimers or heterodimers
- three domains: DNA binding domain, dimerization domain, activation domain
describe regulation by RNA stability
- decapping: exposed mRNA degraded from 5’ end (5’ end serves to protect RNA from RNA degrading enzymes)
- mRNA degraded from 3’ end through poly-A tail and into coding region
Why must post translational medications occur? and what occurs?
so the protein can be functional
proteins fold into 3D conformations with the help of molecular chaperones
co-factors bind
What is the proteasome?
apparatus that deliberately destroys aberrant proteins?
What is the specificity of the proteasome?
one E1 ubiquitin activating enzyme and 1 proteasome but 30 E2 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins
What is methylation and genomic imprinting?
what genes get expressed or not from mom and dad
What is x-chromosome inactivation?
even things out- XX vs XY (2 X chromosomes vs one)
What are the three major checkpoints of the cell cycle?
start: G1 to S
G2 to M
in M phase: anaphase and cytokinesis
Describe the first checkpoint of the cell cycle
start-cell commits to cell cycle entry and chromosome duplication
Describe the second checkpoint of cell cycle
G2/M: move into chromosome alignment on spindle in metaphase
Describe the third checkpoint of cell cycle
metaphase to anaphase transition: triggers sister chromatin separation and cytokinesis
What are Cdks?
heart of cell cycle control system–activities of Cdks rise and fall during cell cycle
What proteins regulate Cdks?
cyclins
Cyclin ____ vary according to point of time in cell cycle
levels
When cyclin is not bound to Cdk, the active site is blocked by what?
region of protein called the T loop
Phosphorylation of Cdk is cased by ____
CAK (Cdk activating enzyme)
What does Wee1 and Cdc25 do to Cdk-Cyclin activities?
Wee1 kinase adds an inhibitory phosphate
Cdc25 phosphatase removes phosphate to activate Cdk
What does CKI (Cdk inhibitory protein do)?
targets G1/S-Cdk and S-Cdks (slide 48)
What are the targets in APC/C?
S-cyclin, M cyclin (slide 48)
What does condensin do?
makes sister chromatids into short structures that can be pulled apart at anaphase with no breakage in 2 steps: chromosome condensation (dramatic compaction) and resolution (sister chromatids become distinct separate units)
What is apoptosis?
programmed cell death
What is the precursor of caspases?
procaspases
What are the two major classes of caspases?
initiator and executioner caspases
What do executioner caspases do?
destroys actual targets–executes apoptosis
REVIEW APOPTOSIS SLIDES
slides 53-58
What are oncogenes?
gain of function, “gas pedal”, involves single mutation event and activation of gene causing proliferation
What are tumor suppressor genes?
lose of function, “brake pedal”, involve genes that inhibit growth. Mutation event: one gene- no effect, second mutation causes problems
What are the ways oncogenes can be activated?
- deletion or point mutation in coding sequence
- regulatory mutation
- gene amplification
- chromosome rearrangment
What are the two major categories of tumor suppressor genes?
- proteins that normally restrict cell growth and proliferation
- proteins that maintain integrity of the genome
What are the two forms of retinoblastoma (Rb)?
hereditary and sporadic
40% of retinoblastoma is hereditary, 60% is sporadic
describe the hereditary form of Rb
loss of function or deletion of one copy of Rb in every cell due to inherited defect, but have one good copy of Rb gene
somatic event occurs: eliminates one good gene, cancer occurs
loss of heterozygosity
describe the sporadic form of Rb
non-cancerous cells fine- no mutation of Rb
two hit hypothesis: first Rb gene obtains mutation then need second mutation Rb
What is a polyp?
precursor of colorectal cancer
