LECT 21:  REGULATED PROTEIN TURNOVER
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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

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LECT 21: REGULATED PROTEIN TURNOVER

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Lect 21 regulated protein turnover

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.


Lect 21 regulated protein turnover

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.


Lect 21 regulated protein turnover

Cbl Terminates Growth Factor Signaling Thru Receptor Ubiquination

EGF

EGF

EGFR

(inactive)

EGFR

(dimerized, phospho-Y)

active

POSITIVE SIGNALING

SIGNAL TERMINATION

Cbl (E3)

Several pathways

activated for growth

or differentiation

Internalization,

ubiquitination,

trafficking to lysosome


Lect 21 regulated protein turnover

Ub

Ub

Ub

Ub

Ub

Ub

Proteasomal Degradation Can Activate Signaling Pathways:

Transcription Via NFkB

Extracellular

Signal

Proteasome

Degradation

IkB

IKK

E3

NFkB

Nuclear Transport

DNA Binding

Transcription Activation


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