Intracellular aminopeptidases and related peptidases (IAPs)

Intracellular aminopeptidases and related peptidases are a group of enzymes, primarily metalloproteases, responsible for the final stages of intracellular protein degradation by cleaving amino acids from the N-terminus of peptides. These enzymes, including Aminopeptidase N (CD13) and Puromycin-sensitive aminopeptidase (PSA), play critical roles in maintaining the intracellular free amino acid pool, regulating the cell cycle, and processing antigens for MHC class I presentation. In oncology, these peptidases are targeted because cancer cells exhibit a heightened dependency on protein recycling to sustain rapid proliferation and protein synthesis. Inhibition of these enzymes, notably by the drug Tosedostat, induces an amino acid deprivation response and cellular stress, leading to apoptosis in malignant cells while sparing normal tissues to a degree. Beyond cancer, these enzymes are involved in inflammatory processes and the regulation of bioactive peptides, making them versatile targets for therapeutic intervention.

Other names

Intracellular aminopeptidasesCytoplasmic aminopeptidasesM1 family aminopeptidasesAminopeptidase N (CD13)Puromycin-sensitive aminopeptidase (PSA/NPEPPS)Leukotriene A4 hydrolase (LTA4H)Endoplasmic reticulum aminopeptidase 1 (ERAP1)Endoplasmic reticulum aminopeptidase 2 (ERAP2)

Inhibition of aminopeptidase activity leads to the depletion of the intracellular free amino acid pool, triggering an amino acid deprivation response (AADR), cellular stress, and apoptosis, particularly in rapidly dividing cancer cells.