ANHB3323 Lecture Notes - Lecture 4: Second Messenger System, Tumor Suppressor Gene, Gsk3B

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LECTURE FOUR: Control of Gene Expression Signaling and the
Environment
The Human Genome:
DNA encodes proteins that determine cell structure and function
Any given cell expresses only a subset of its genes
A cell’s function is defined by the subset of genes it expresses
During development each cell’s environment affects its gene expression
Control of Gene Expression:
In the adult, stem cells and differentiated cells all need to control their
genes
Stem cells have to combine proliferation and renewal with differentiation
when needed
Once cells differentiate they have a finite life also must respond
appropriately to the environment
Diseased cells (e.g. cancer) change their program to allow uncontrolled
growth, cope with stress and take best advantage of their environment
How Do Cells Respond to their Environment?
Signaling chemical and mechanical
Receptors
Intermediaries influencing post translational modifications
Nuclear translocation/nuclear import
Most pathways end with the nucleus and gene regulation
Chemical Messengers:
Include growth factors, hormones, neurotransmitters and extracellular
matrix components
Effects can be exerted locally or at great distances elsewhere in the body
e.g. hormones vs. synaptic vesicles
Messengers have to interact with the plasma membrane
Membrane Receptors:
Required for most extracellular signals
Either membrane bound proteins or intracellular receptors
Intracellular receptors bind signaling molecule if signal is lipid soluble
e.g. estrogen signaling
Once bound by their substrate the receptors move into the nucleus
Regulate gene expression by binding to DNA elements in the promoters of
target genes
Cell Surface Receptors:
Non-lipid soluble signaling molecules cell surface receptors
GPCR G-protein coupled receptors
o Multiple signaling pathways/ligands
o Binding to GPCR activates effector enzymes through
conformational change (GDP GTP)
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Document Summary

Lecture four: control of gene expression signaling and the. How do cells respond to their environment: signaling chemical and mechanical, receptors, nuclear translocation/nuclear import, most pathways end with the nucleus and gene regulation. Include growth factors, hormones, neurotransmitters and extracellular matrix components: effects can be exerted locally or at great distances elsewhere in the body. E. g. hormones vs. synaptic vesicles: messengers have to interact with the plasma membrane. Membrane receptors: required for most extracellular signals, either membrane bound proteins or intracellular receptors. Cell surface receptors: non-lipid soluble signaling molecules cell surface receptors, gpcr g-protein coupled receptors, multiple signaling pathways/ligands, binding to gpcr activates effector enzymes through conformational change (gdp gtp, triggers signaling cascade, important in cancer. Signal transduction cascades: used to transmit signal from surface to nucleus. Apoptosis signaling: mitochondria important to apoptosis, release cytochrome c when compromised, cytochrome c activates caspase 9 top protease that activates proteases.

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