Protein arginine methyltransferase 1 interacts with Gli1 and regulates its transcriptional activity

Tumour Biol. 2016 Jul;37(7):9071-6. doi: 10.1007/s13277-015-4754-7. Epub 2016 Jan 13.

Abstract

Protein arginine methylation, which is mediated by the protein arginine methyltransferases (PRMTs), is associated with numerous fundamental cellular processes. Our previous studies have shown that PRMT1 activated Hedgehog signaling in the esophageal squamous cell carcinoma (ESCC) cells and promoted the growth and migration of cancer cells. However, the detailed mechanisms are unknown. In this study, it was found that PRMT1 interacted with the transcriptional factor Gli1 (glioma-associated oncogene homolog 1) in ESCC cells. The DNA-binding domain (DBD) of Gli1 is responsible for its interaction with PRMT1. Moreover, PRMT1 promoted the methylation of Gli1, and knocking down the expression of PRMT1 impaired the transcriptional activity as well as the biological functions of Gli1. Taken together, our study demonstrated that PRMT1 is a positive regulator of Hedgehog signaling, and PRMT1 might be a therapeutic target for ESCC.

Keywords: ESCC; Gli1; Methylation; PRMT1.

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Cell Line, Tumor
  • DNA Methylation / genetics
  • DNA-Binding Proteins / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Squamous Cell Carcinoma
  • Hedgehog Proteins / genetics
  • Humans
  • Protein-Arginine N-Methyltransferases / genetics*
  • Repressor Proteins / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics*
  • Transcriptional Activation / genetics
  • Zinc Finger Protein GLI1 / genetics*

Substances

  • DNA-Binding Proteins
  • GLI1 protein, human
  • Hedgehog Proteins
  • Repressor Proteins
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases