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Gene Expression and cell function/ structure (Cancer (Cell Communication…
Gene Expression and cell function/ structure
Protein Processing and modification
Co-Translational
ER signal Sequence
Secreted or organelle targeted proteins
Encode a signal sequence that targets to the ribosome in the ER
Remain in Cytosol
Targeted to organelles
Nuclear Proteins
contain a specific sequence of amino acids called a nuclear localization signal sequence.
Post-Tranlational modification
Proteolysis
cleaving the polypeptide allows the fragment to fold into different shapes
Glycosilation
Adding sugars is important for targeting and recognition
Most common form of post translational processing
most glycosilated proteins either remain in membrane or secreted
Phosphorylation
Added phosphate groups alter the shape of protein
A phosphate is added by kinase enzyme which can be removed by phosphatases
Ubiquitation
Ubiquitin is added to a protein that is to be degraded- marks it for destruction in a proteasome
Co-Translational Protein Sortin
SRP binds to the ER signal sequence and pauses translation in the ribosome.
SRP binds to receptor in the ER membrane
SRP is released and translation resumes in the ER where the polypeptide extrudes into the lumen.
ER signal sequence is cleaved by signal peptidase
The polypeptide is completely synthesized in the lumen where it enters a vesicle.
The vesicle leaves the ER and enters the golgi where it is sorted and taged for its destination
7.The vesicle leaves the golgi and the protein fuses itself into the membrane of the vesicle allowing for facilitated delivery into different areas in the cell.
EX. can be targeted to the lysosome by being tagged with mannose 6 phosphate (M6P)
A mutated phosphotrasnferase is unable to transfer the phosphate to mannose on these proteins failing to target the lysosome and being excreted outside of the cell.
MLII, I-Cell disease
Membranes and Transport proteins
Phospholipid Bilayer
Phospholipids can move in several ways
Lateral
Flipping
Rotaional
Diffusion
Passive Transport
Simple Diffusion
Facilitated Diffusion
Active Transport
Involves the hydrolysis of ATP.
Can transport against a concentration gradient
Co-Trasnport
Symports- two molecules entering the cell at the same time.
hydrogen sucrose symporter.
Potassium and Sodium pump
Transports 3 sodium out and 2 potassium in
Ion Channels
Most are passive and specific. Gated and open only under certain conditions
Channelopathies
Molecular mechanisms of channel disruption
Cystic Fibrosis
Accumulation of mucus in lungs leads to deadly infections
Due to lack of function of a functional CFTR transporter of chloride ions (recessive loss of function)
Over 50% of Cystic Fibrosis case have delta F508 which has a single codon deletion disrupting protein sorting
Lack of fucntional Chloride anion channel protein
CFTR channels have limited lifespan and eventually are removed
Total CFTR activity depends on quantity and function.
Heterozygous individuals produce enough of the protein for normal lung fucntion
Aquaporins
passive membrane channel proteins
permit cellular water flow (osmosis)
AQP5- important in producing sweat and tears and secretions in the lung
In responses to osmotic triggers, cells can quickly change membrane permeability to water by increasing number of aquaporins.
Stimulated insertion of membrane vesicles containing pre-fromed aquaporins into the plasma membrane
Cancer
Most common causes are treatable (Breast and Prostate)
Deadliest includes Lung and Pancreatic cancer
Describes a collection of diseases resulting from unregulated cell division.
Cells divide in order to grow or replace damaged cells
An imbalance in this leads to increased cell division or decreased apoptosis
Checkpoints controll the cell cycle
Cell growth checkpoint (is environment favorable)
2.DNA synthesis Checkpoint (has the DNA been replicated correctly)
Checkpoints are cyclin dependent kinases and cyclins
CDK only function when bound to cyclins
CDK/cyclin complexed phosphorylate target proteins
They are specilaized
Cyclin degradation leads to irreversible end of the cell cycle
3.Mitosis Checkpoint (are the chromosomes attached to the spindle)
Cancer Cells ignore the normal cell cycle checkpoints
Cancer "Genes"
Tumor suppressor genes
Normally these genes act like breaks slowing cell division and preventing genome instability
Recessive loss of function mutation leads to cancer
BRCA1 a tumor suppressor gene associated with inherited predisposition to breast cancer
Shows dominant predisposition to cancer when familial pedigree is observed
Proto-Oncogenes
Normally these genes act like the gas pedal; proto-oncogene needed for cell cycle progression
Dominant gain of function leads to oncogenes which lead to cancer.
Cancer forms as one cell accumulates mutations
Cancer cells have many mutations but only some of those are in cancer causing genes
Enzymatic systems may be damaged and prevent the repairing of DNA damage
Look and behave differenly
Grow into tumors due to lack of contact inhibition mechanism
Autocrine stimulation
Loss of apoptosis
Anglogenesis
Signal blood vessels to grow and provide the cancer with nutrients
Metastasize
Travel around the body and spread
Cell Communication Pathway
Signal/ Growth Factor binds to the receptor in the cells membrane
Signal is transduced after stimulating growth factor is processed by the receptor
Expression of protein that stimulates cell division is carried out after the transducers act as activators for the enhancer
RB Tumor Supressor gene delays cell cycle progression into the S phase
Growth factor binds to the receptor
Signal transduction activated expression of cyclin D and E
CDK/ cyclin D phosphorylates Rb
E2F (activator) freed to activate genes needed for DNA synthesis
Unphosphorylated Rb inhibits E2F transcription factor from activating gene synthesis
Rb tumor supressor gene
Tumor in eye caused by the deletion of Rb gene (Retinoblastoma)
Fucntion lost by
2.DNA methylation near promoters of tumor suppressor genes inhibit trasncription
Aneuploidy chromosomes leads to the lose of one or more tumor suppressor genes
A Mutation in the tumor suppresor gene itself
Ras, a proto-onco gene (G-Protein) that promotes cell cycle progression
Protein kinases carry after GTP is transformed to GDP
Activator able to attach and the protein stimulate cell cycle.
Receptor protein leads to the creation of Ras and GTP construct
GTP re-attaches to RAS preventing it from continuing the stimulus
Growth factor attaches to the receptor protein
The Tyrosine kinase inhibitor Gleevec is used to treat CML by allowing the drug to attach with higher affinity to the enzyme and preventing phosphorylation of the target proteins that cause leukemia.
Can occur sporadic ( spontaneuous) or inherited which prediposes organism to a higher chance of developing cance rin his or her lifetime.
Sporadic cases of cancer DONT increase the inheritability of cancer (O%)