DNase I behaves as a transcription factor which modulates Fas expression in human cells

Mara Oliveri, Antonio Daga, Claudio Lunardi, Riccardo Navone, Romano Millo, Antonio Puccetti

Research output: Contribution to journalArticle

Abstract

DNase I is the major nuclease present in biological fluids and is ubiquitously expressed in mammalian tissues. It is responsible for the removal of DNA from nuclear antigens, and consistently with this function, DNase I-deficient mice show features of autoimmunity. The enzyme seems also to be involved in apoptosis (programmed cell death). We demonstrate that DNase I is internalized by human cells upon binding mannose 6-phosphate receptor and gains access into the cells. Following internalization of the enzyme, the cells show an increased surface expression of Fas molecule, a key regulator of apoptosis. Here we show that DNase I up-regulates fas transcription upon interaction with the fas gene promoter. Moreover, overexpression of the DNase I gene in human cells results in a similar modulation of the fas gene expression. Our data provide the first evidence that the endonuclease DNase I behaves as a transcription factor which selectively regulates cell surface Fas expression in human cells and point towards a fundamental role of DNase I in the regulation of the apoptotic machinery.

Original languageEnglish
Pages (from-to)273-279
Number of pages7
JournalEuropean Journal of Immunology
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Apoptosis
  • DNase I
  • Fas
  • Transcription factor

ASJC Scopus subject areas

  • Immunology

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