Differential processing of mammalian L-histidine decarboxylase enzymes

Biochem Biophys Res Commun. 2014 Mar 7;445(2):304-9. doi: 10.1016/j.bbrc.2014.01.178. Epub 2014 Feb 4.

Abstract

In the mammalian species studied so far, the L-histidine decarboxylase (HDC) enzyme responsible for histamine biosynthesis has been shown to undergo post-translational processing. The processing is best characterized for the mouse enzyme, where di-asparate DD motifs mediate the production of active ~55 and ~60 kDa isoforms from the ~74 kDa precursor in a caspase-9 dependent manner. The identification of conserved di-aspartate motifs at similar locations in the rat and human HDC protein sequences has led to proposals that these may represent important processing sites in these species also. Here we used transfected Cos7 cells to demonstrate that the rat and human HDC proteins undergo differential processing compared to each other, and found no evidence to suggest that conserved di-aspartate motifs are required absolutely for processing in this cell type. Instead we identified SKD and EEAPD motifs that are important for caspase-6 dependent production of ~54 and ~59 kDa isoforms in the rat and human proteins, respectively. The addition of staurosporine, which is known to pharmacologically activate caspase enzymes, increased processing of the human HDC protein. We propose that caspase-dependent processing is a conserved feature of mammalian HDC enzymes, but that proteolysis may involve different enzymes and occur at diverse sites and sequences.

Keywords: Caspase cleavage site; Caspase-6; Histamine biosynthesis; Histidine decarboxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • COS Cells
  • Caspase 9 / metabolism*
  • Chlorocebus aethiops
  • Histidine Decarboxylase / chemistry
  • Histidine Decarboxylase / genetics*
  • Histidine Decarboxylase / metabolism*
  • Humans
  • Mice
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Species Specificity
  • Transfection*

Substances

  • Protein Isoforms
  • Recombinant Proteins
  • Caspase 9
  • Histidine Decarboxylase