Post on 05-Feb-2016
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LECT 21: REGULATED PROTEIN TURNOVER
Cellular proteins have different stabilities. It is the combination of synthesis and degradation rates that determines the level of a protein in a cell, and changes in either rate can serve as means to regulate a protein’s concentration in the cell.
Protein degradation in response to extracellular signals is an important component of some intracellular signaling pathways.
Protein degradation is further required to mis-folded or de-folded proteins, which would otherwise be capable of forming insoluble aggregates.
Machinery for Protein Degradation Within Cells
Cytosolic proteins targeted for degradation are digested in the 26S proteasome, a large multienzymatic structure.
Membrane proteins targeted for degradation travel through endosomes to the lysosome, whose lumen contains a collection of proteases.
Both targeting processes employ the covalent tagging of proteins with ubiquitin, a small 76 amino acid polypeptide.
EGF
EGFR(inactive)
EGFR(dimerized, phospho-Y)
active
EGF
POSITIVE SIGNALING SIGNAL TERMINATION
Cbl (E3)
Several pathwaysactivated for growth
or differentiation
Internalization,ubiquitination,
trafficking to lysosome
Cbl Terminates Growth Factor Signaling Thru Receptor Ubiquination
Proteasomal Degradation Can Activate Signaling Pathways:Transcription Via NFB
UbUbUbUbUbUb
UbUbUbUbUbUb
Nuclear TransportDNA Binding
Transcription Activation
ProteasomeDegradation
NFB
IB
ExtracellularSignal
IKK E3