Regulation of tumor necrosis factor- and Fas-mediated apoptotic cell death by a novel cDNA, TR2(L)

Hong Cao, Jeffery Mattison, Yi Zhao, Nicole Joki, Michael Grasso, Nan Shan Chang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A novel cDNA, TR2(L), isolated from murine NIH 3T3 fibroblasts, was found to modulate tumor necrosis factor (TNF)-mediated apoptosis in murine L929 fibrosarcoma cells. The full-length cDNA (853 bp) encodes a predicted coding region of 56 amino acids (6.3 kD), with 53.6% identity to the C-terminus of rat transcriptional activator FE65. When expressed stably in L929 cells, TR2(L) protein inhibited TNF cytotoxic response. In contrast, TR2(L) enhanced anti-Fas antibodies/actinomycin D (ActD)-mediated L979 apoptosis. Alteration of TR2, function occurred by tagging this protein with a 6xHis fragment to the N-terminus (designated 6xH-TR2(L)). L929 cells which stably expressed 6xH-TR2(L) acquired a significantly enhanced TNF apoptotic response and increased genomic DNA fragmentation compared to control cells. Enhanced cell death also occurred in these 6xH-TR2(L)-expressing cells under serum starvation conditions. In contrast, the anti-Fas/ActD-mediated apoptosis was blocked by the 6xH-TR2(L) protein. Functional role of TR2(L) protein in regulation of cancer cell susceptibility to TNF- and Fas ligand-mediated apoptosis is suggested.

Original languageEnglish
Pages (from-to)266-272
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume227
Issue number1
DOIs
Publication statusPublished - 1996 Oct 3

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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