Week One Flashcards
What is cellular stress response
Referred to the complex set of signalling reaction’s in cells ranging from activation of pathways that promote cell survival to eliciting programmed cell death that eliminated damaged cells
What are the three groups of stress
Environmental
Physiological
Pathological
What are examples of environmental stress
cell surroundings temperature, oxidants, change in concentration of ions outside the cells
What are examples of physiological stress
regular life cycle or cell functioning responses to growth factors, hormones (gym workout)
What are examples of pathological stress
Associated with many diseases cancer tissues, low ph due to high metabolic rate, fever,diabetes
what is adapative stress response
They want to activate specific signaling mechanisms to restore homeostasis choice between cell survival and cell death is a central conceptual point for signaling mechanisms
What is common cell responses
There are common cell responses to stress chaperons, global reduction of protein translation, and glycosylation and remodelling cellular cytoskeleton
What are the three common components of adaptive stress response pathways
Sensor
Trandcuer
Transcrption factors
What is the sensor
Protein that physically interacts with TF in the cytosol under normal conditions and stops it from moving into the nucleus or degrades it so it can not interact with stress sensitive genes
What is the transducer
It is an enzymatic protien that is activated by stress and covalently modify the TF/sensor complex which inhibit sensor function the TF then goes into the nucleus which the cell needs the genes for the stress response or apoptosis
What happened with Transgensic mice
Delte genes encoding the sensor or the TF compontents demonstrated serious biological consequences
What was found when the genetic information on the sensor was deleted
It was leathal in all cases
What does it mean when you knock out the sensor
Removes the negative feedback on TF and TF is overexpressed
What happens when you delete only TF
Animals can surrvive
What happens when you delete both the sensor and TF
It is lethal crosstalk between different signalling pathways
What is a common response of cells to stress
Global reduction of protein synthesis helping cells to not waste energy needed to overcome stress
What is the mechanisms that leads to the overall decrease in protiein synthesis
Phosphorylation of the alpha subunit of elF2 which is induced by stress specefic kinases
What is elF2
A trimeric GTP-binding protein that delivering initiator methionyl-tRNA to the small 40S ribsomal complex for initation
What can bind to the elf2a subunit
GDP or GTP
What does GTP-elf2 complex bind to
Met-tRNAi
What is the 43S preinitation complex
The elF2 complex that is bound to Mer-tRNAi and associates with the 40S ribosmoal subunit and additional regulatory factors
What happens when with stress induced phosphorylation of elF2
It lowers general protien translation which allows cells to correct the stress damage and ATF4
How is the translation of stress related proteins such as ATF4 is stimulated, while the global protein synthesis is reduced or inhibited
Delayed translation reinitation upstream open reading frames
What happens in non-stressed conditions
Low levels of elF2-P and high levels of elF2-GTP. Ribsome binds to the ATF4 and translation of uORF1 which then initates the next uORF2 which overlaps out of rame with ATF4 it then misses the start codon so you no longer have ATF4
What happens during cellular stress
More elF2-P low elF2-GtP . Translation initation complex is not assembled. It takes longer for the 40s ribsomal unit to reacuire a new elF2 that you need for uORF2 the ribsome scans pass it that the ATF4 scan past it
What is no stress condtions
High elf2-GTP Low elF2a-P
What is Stress condtions
Low elF2-Gtp and High elF2a-P
