Dipeptidyl carboxypeptidase I

Dipeptidyl Carboxypeptidase I (DCP1), also known as Cathepsin C or Dipeptidyl Peptidase I (DPPI), is a lysosomal enzyme that plays a crucial role in the activation of various serine proteases within immune and inflammatory cells. This enzyme is particularly significant in the processing of granule-associated serine proteases in neutrophils, macrophages, and natural killer cells, which are essential for the immune system's response to infection and inflammation.

Function

Dipeptidyl Carboxypeptidase I is involved in the removal of dipeptides from the N-terminus of protein substrates. This action is critical for the activation of several serine proteases, including granzymes, cathepsin G, and neutrophil elastase, which are involved in the immune response. By activating these proteases, DCP1 facilitates the maturation of immune cells and the degradation of pathogens, playing a vital role in the body's defense mechanism.

Genetic and Molecular Structure

The gene encoding Dipeptidyl Carboxypeptidase I is located on chromosome 11q14.1-14.3. The enzyme is synthesized as an inactive precursor, which undergoes processing in the lysosome to become active. The active form of DCP1 is a tetramer, composed of four identical subunits, each containing a heavy and a light chain that are derived from the same precursor protein.

Clinical Significance

Mutations in the gene encoding DCP1 can lead to a rare autosomal recessive disorder known as Papillon-Lefèvre Syndrome (PLS), characterized by severe periodontitis and palmoplantar keratoderma. Additionally, deficiencies in DCP1 activity have been associated with increased susceptibility to bacterial infections, due to the impaired activation of serine proteases and subsequent reduction in the immune response.

Research and Therapeutic Potential

Research into Dipeptidyl Carboxypeptidase I has focused on understanding its role in immune regulation and inflammation. Given its crucial role in activating serine proteases, DCP1 is a potential target for therapeutic intervention in diseases characterized by excessive inflammation or immune dysregulation. Inhibitors of DCP1 could potentially modulate the immune response, offering new avenues for the treatment of inflammatory diseases and certain immune disorders.