Term
| Functions of Protein Turnover (5) |
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Definition
1)Serve as energy source, esp. during starvation
2)Rid cell of defective proteins
3)Turnover of extracellular signals
4)Regulate levels of proteins, esp during the cell cycle
5)Important role in antigen presentation |
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Term
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Definition
Half-life, max is 24hrs.
1)Requires energy
2)Often regulated |
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Term
| Freshly made (de novo) proteins require chaperones |
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Definition
-Hsp40, Hsp70, and Hsp90 (end of the line) are required.
-HSP90 can either mark protein for preservation or degradation.
-Degradation of Hsp90 results in protein degradation. |
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Term
| Proteins that become damaged, or unfolded due to stress, are also regulated by chaperones. |
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Definition
-Unenergetically favorable for protein to stay unfolded.
-Energetically favorable for oligmers to form and REALLY energetically favorable for amyloid fibrils to form. |
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Term
| Different things that can happen to proteins if chaperones are disassociated. |
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Definition
1)Chaperones can be disrupted by a)heat shock or stress
2)Protein can aggregate (reversible)
3)Protein can fold (reversible)
4)Protein can get degraded (irreversible) |
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Term
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Definition
Hsp90 inhibitors block the ATPase activity of Hsp90 (binds where ATP should go):
1)Currently in clinical trials for cancer.
2)Currently in pre-clinical development with pharma for neurodegenerative diseases. |
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Term
| What are all of these “osomes”? |
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Definition
1)Endosome – a membraned organelle that transports things in the cell *it's all good*
2)Phagosome – a membraned organelle that was derived from the plasma membrane and now contains a foreign object or old proteins from the cell surface *get off my lawn*
3)Phagosome and endosome are sometimes used interchangeably
4)Lysosome – a membraned organelle that contains the enzymes and acidic environment necessary to degrade most proteins (LYSOSOMAL DEGRADATION=
**AUTOPHAGY**) *Is that a Big Kahuna burger?-Bad mother. I'll mother fucking eat you!*
5)autophagosome – a membraned organelle that has engulfed parts of the cytoplasm, proteins and all *You're pretty funny for a guy with 9 fingers.*
6)Autophagolysosomes form when lysosomes fuse with autophagosomes
7)Endosome/Phagosome buds from surface and combines with lysosome which buds from the golgi to form a phagosome followed by degradation of the contents of the endosome. |
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Term
| Autophagy; 3 distinct pathways |
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Definition
1)Chaperone-mediated autopathy (LAMP-2A is a receptor)
2)Microautophagy (when things are bad locally in the same)
3)Macroautophagy (another variant of cell death) |
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Term
| Lysosomal/Endosomal Protein Turnover |
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Definition
1)Usually involves proteins endocytosed
2)Takes place in acidic environment
3)Requires energy for proton pump on endosomal membrane
4)Involved in turnover of extracellular ligands
5)Involved in processing of extracellular antigens
*An example: Uptake and turnover of LDL via the receptor mediated pathway of endocytosis.
If you overwhelm the system, you get LDL build-up.* |
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Term
| Autophagy is involved in (7) |
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Definition
1) Myopathies
2) Neurodegeneration
3) Cancer
4) Ageing *no cons!*
5) Liver disease
6) Heart disease
7) Infection and immunity *Rapamycin, immunosuppressant, activates autophagy and may be implemented in Alzhemiers.* |
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Term
| Proteasome-Mediated Protein Turnover |
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Definition
1)Almost always requires prior ubiquitination of target protein
2)Ubiquitination requires energy
3)E3 Ubiquitin ligase determines specificity
4)Proteasome involved in turnover of cyclins, misfolded proteins, etc.
5)Degradation is not always complete |
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Term
| Connection ubiquitin makes to connect to residues |
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Definition
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Term
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Definition
1)Tau typically stabilizes microtubules and when it is ubiquinated, you have formation of PHF which causes Alzheimer's (cell can't clear it).
2)CHIP; E3 Ubiquitin Ligase involved in Alzheimer’s disease
3)CHIP antibody stains NFT lesions in Alzheimer’s brain--CHIP can't ubiquinate tau. |
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Term
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Definition
| The human papilloma virus produces a protein (E6) that acts as an E3 ubiquitin ligase. It triggers the ubiquitination and turnover of p53. |
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Term
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Definition
1)Protein turnover is a first order process that requires energy and is often regulated.
2)Endosomes/Lysosomes are involved in turnover mostly of extracellular proteins.
3)Many proteins are turned over by being tagged with ubiquitin and degraded by the proteasome. Ubiquitin ligases determine which proteins are to be degraded. |
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