Lecture 30 - Cytoplasm Stress Response Flashcards
What is the purpose of the stress responses of eukaryotic cells?
eukaryotic cells respond by:
Adapting to stress.
Alleviating stress.
Killing itself in the face of extreme or ongoing stress.
What are the types of abiotic stress?
Extracellular:
Altered temperature
Deprivation of oxygen/nutrients
exposure to different forms of radiation
exposure to oxidising agents or alkylating agents
changes in pH and osmolarity
Intracellular:
Byproducts of metabolism such as ROS which can damage intracellular molecules.
Proteins may be misfolded in the ER or mitochondria.
*Extracellular stresses can alter intracellular conditions and cause intracellular stress as well.
What are acute stresses?
Stresses that are transient in nature. Cell need to tolerate them for a small amount of time to survive.
What are chronic stresses?
Stresses that are persistent for a long time and include pathological or developmental processes and they require long-term changes in cells.
What is the general response to heat that was initially seen in drosophilla?
Chromosomes puff up in drosophilla during heat shock.
This resulted in transcription of Heat Shock Factors which were activated in response to heat.
Heat shock proteins were transcribed as well which are chaperone-type proteins involved in cytoprotection.
What happens to heat shock protein levels during elevated temperatures?
Heat shock proteins are present in normal circumstances in small amounts. After heat shock the heat shock protein levels are elevated.
How is HSF1 activated by heat?
HSF1 is inactive under normal circumstances and is held in this state by heat shock proteins.
2) Heat shock protein is released in response to heat to attach to denatured proteins and as a result HSF1 proteins are activated to transcribe more of their inhibitors (Hsp70). This response is as strong as required and is modulated by reciprocal inhibition.
* This is most likely driven by equilibrium being driven to binding to misfolded proteins rahter than affinity.
What are the domains of HSF1 that are important for its response to heat?
HSF1 is a multidomain protein;
It contains a DNA binding domain, (DBD)
TAD is the domain that increases transcription of target proteins like the heat shock proteins. Activation of this protein results in a trimeric protein and it interacts with a very specific DNA sequence which it can bind to with its DBD domain.
Regulatory Domain contains multiple residues that are subject to modification (Phosphorylation, Acetylation, Sumoylation, etc..)
How does transcription machinery respond to binding of HSF1?
Transcription machinery is ready at the heat shot transcription location. HSF1 binding to HSE region results in transcription to take place.
