Caspases all cleave on the carboxyl side of an aspartate residue. The mechanism is thought to involve deprotonation of a cysteine sulfhydryl by an adjacent histidine residue, followed by nucleophilic attack of the cysteine sulfur on the peptide carbonyl carbon. Proteins with N-terminal Met, Ser, Ala, Thr, Val, or Gly have half lives greater than 20 hours. Proteins with N-terminal Phe, Leu, Asp, Lys, or Arg have half lives of 3 min or less. Regulatory proteins are degraded at particular phases of the cell cycle, or in response to internal or external signals.
Some protein degradation occurs in lysosomes .
Lysosomes contain several different proteases, with acid pH optima, called cathepsins . Lysosomes degrade proteins taken in by endocytosis . In a process called autophagy , a membrane may enclose part of the cytoplasm. Fusion of the resulting vacuole with a lysosome may result in degradation of enclosed cytoplasmic macromolecules. This mechanism does not allow selective degradation of individual proteins.