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