Studies on the biological functions of CPS1 in AFB1 induced hepatocarcinogenesis

Gene. 2016 Oct 10;591(1):255-261. doi: 10.1016/j.gene.2016.07.031. Epub 2016 Jul 15.

Abstract

Carbamyl phosphate synthetase 1 (CPS1) was down-regulated in hepatocellular carcinoma (HCC), as treated by aflatoxin B1 (AFB1), a potent hepatocarcinogenesis mycotoxin. In this study, we firstly confirmed that AFB1 down-regulated the expression of CPS1 in a dose-dependent manner. At the meantime, both siRNA knock down of CPS1 and AFB1 treatment inhibited cell proliferation, and induced cell apoptosis. To further analysis the function of CPS1, the interacting proteins of CPS1 were searched by Co-IP, and three interacting proteins including type II cytoskeletal 1 (KRT1), albumin (ALB), and ubiquitin C (UBC) were found. Both KRT1 and ALB were new interacting proteins for CPS1. Our further study showed that CPS1 was regulating interacted and colocalized with KRT1 and ALB, and the intensity correlation was changed by AFB1. KRT1, ALB and CPS1 were all reported to play an important role in differentiation and tissue specialization. These results may offer an increasing understand that CPS1 might have a function in differentiation.

Keywords: Aflatoxin B(1); Carbamyl phosphate synthetase I; Hepatocarcinogenesis; Interacting protein.

MeSH terms

  • Aflatoxin B1 / metabolism*
  • Albumins / metabolism
  • Carbamoyl-Phosphate Synthase (Ammonia) / metabolism*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Humans
  • Immunoprecipitation
  • Keratin-1 / metabolism
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology
  • Mass Spectrometry
  • Protein Binding

Substances

  • Albumins
  • Keratin-1
  • Aflatoxin B1
  • Carbamoyl-Phosphate Synthase (Ammonia)