Endogenous protein breakdown is the catabolism of a cell's own proteins, occurring primarily in proteasomes and lysosomes.

Reasons for degrading endogenous protein:

• Regulation through turnover: degrade the right protein at the right time.
• Quality control: misfolded, mistranslated, or error-containing proteins. Chaperones first attempt correction; if that fails, lysosomes and proteasomes degrade the protein.
• Source of amino acids: released amino acids serve as fuel and as anabolic precursors.

Sequence features influence protein half-life:

• The N-terminal residue affects longevity (e.g., an N-terminal serine gives a long half-life of >20 hours, whereas aspartate gives a very short one of <3 minutes).
• A PEST sequence (rich in proline (P), glutamate (E), serine (S), and threonine (T)) marks a protein for rapid turnover; its residues may be phosphorylation sites that promote recognition by the ubiquitination machinery.

Key step: ubiquitination tags the target protein for proteasomal degradation.