A Critical Role for Cysteine 57 in the Biological Functions of Selenium Binding Protein-1

Int J Mol Sci. 2015 Nov 18;16(11):27599-608. doi: 10.3390/ijms161126043.


The concentration of selenium-binding protein1 (SBP1) is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies indicated that cysteine 57 is the most likely candidate amino acid for selenium binding. In order to investigate the role of cysteine 57 in SBP1, this amino acid was altered to a glycine and the mutated protein was expressed in human cancer cells. The SBP1 half-life, as well as the cellular response to selenite cytotoxicity, was altered by this change. The ectopic expression of SBP1(GLY) also caused mitochondrial damage in HCT116 cells. Taken together, these results indicated that cysteine 57 is a critical determinant of SBP1 function and may play a significant role in mitochondrial function.

Keywords: glutathione peroxidase 1; mitochondrial damage; selenite cytotoxicity; selenium-binding protein1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Codon*
  • Cysteine / chemistry
  • Cysteine / genetics*
  • Cysteine / metabolism*
  • Gene Expression
  • Glutathione Peroxidase / metabolism
  • HCT116 Cells
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Protein Binding
  • Proteolysis
  • Selenium / toxicity
  • Selenium-Binding Proteins / chemistry
  • Selenium-Binding Proteins / genetics*
  • Selenium-Binding Proteins / metabolism*
  • Signal Transduction / drug effects


  • Antineoplastic Agents
  • Codon
  • SELENBP1 protein, human
  • Selenium-Binding Proteins
  • Glutathione Peroxidase
  • Selenium
  • Cysteine