Positive regulation of Fas gene expression by MSSP and abrogation of Fas-mediated apoptosis induction in MSSP-deficient mice

Exp Cell Res. 2005 May 1;305(2):324-32. doi: 10.1016/j.yexcr.2005.01.006.


MSSP has been identified as a transcription factor that regulates the c-myc gene. MSSP was later found to positively or negatively regulate a variety of genes, including alpha-smooth actin, MHC class I, MHC class 2 and the thyrotropin receptor. The knockout mice for the Mssp gene developed by us revealed that these mice became partially embryonic lethal due to a low concentration of progesterone at E2.5. In this study, we further analyzed Mssp-knockout mice and found that the expression of the Fas gene was repressed, resulting in abrogation of Fas-mediated induction of apoptosis both in Mssp-knockout mice and primary thymocytes. MSSP was then found to stimulate promoter activity of the Fas gene by binding to a region spanning -1035 to -635 in chromatin immunoprecipitation assays. Binding of MSSP in the MSSP-binding sequence, TCTAAT, located in this region was confirmed by mobility shift assays, and deletion of this sequence from the Fas promoter was found to result in loss of MSSP-dependent stimulating activity. The results suggest that MSSP is an important mediator for Fas-induced apoptosis in vivo and in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Endolyn
  • Gene Expression Regulation*
  • Genes, Reporter / genetics
  • Humans
  • Luciferases / analysis
  • Luciferases / genetics
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Sequence Deletion
  • Thymus Gland / cytology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • fas Receptor


  • Cd164 protein, mouse
  • DNA-Binding Proteins
  • Endolyn
  • Fas protein, mouse
  • Receptors, Tumor Necrosis Factor
  • Transcription Factors
  • fas Receptor
  • Luciferases

Associated data

  • GENBANK/L11289