How do cells monitor their thousands of different proteins for degradation?

1. There are many different features of proteins that indicate they should be
degraded.
2. There are hundreds of E3 proteins with different recognition-specificities.

Exposed hydrophobic patch.

Exposed specific amino acid sequence motif

Destruction Box
PEST sequence

Many proteins are phosphorylated by a protein kinase to target them for degradation.
The phosphate group results in the exposition of a specific amino acid sequence.

N-end Rule: the N-terminal amino acid determines stability. Certain N-terminal
amino acid residues are destabilizing.

Others….
Avram Hershko