GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA cascade in colitis

Apoptosis. 2016 Dec;21(12):1386-1397. doi: 10.1007/s10495-016-1301-y.


Glycinamide ribonucleotide formyltransferase (GART) has been established as a pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in many diseases. We aimed to investigate the role of GART in the pathogenesis of Crohn's disease (CD). In our study, we demonstrated for the first time that GART expression is up-regulated in patients with active CD and in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the inhibition of GART induced cellular apoptosis and suppressed the migration of IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated protein kinase (MAPK) pathway, following with the dys-regulation of p53 and p53 up-regulated modulator of apoptosis (PUMA). Taken together, GART plays a critical role in the protection of cellular apoptosis and migration of intestinal epithelial cells to maintain the integrity of the epithelial barrier, thus providing a new potential approach in designing a novel therapy for CD.

Keywords: Apoptosis; Crohn’s disease; Glycinamide ribonucleotide formyltransferase; Intestinal epithelial cells; P38; P53.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Carbon-Nitrogen Ligases / genetics
  • Carbon-Nitrogen Ligases / metabolism*
  • Cell Proliferation
  • Colitis / enzymology
  • Colitis / genetics
  • Colitis / metabolism*
  • Colitis / physiopathology
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology
  • Epithelial Cells / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / cytology
  • Intestines / enzymology
  • MAP Kinase Signaling System
  • Phosphoribosylglycinamide Formyltransferase / genetics
  • Phosphoribosylglycinamide Formyltransferase / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Phosphoribosylglycinamide Formyltransferase
  • p38 Mitogen-Activated Protein Kinases
  • Carbon-Nitrogen Ligases
  • GART protein, human