TY - JOUR
T1 - DNase I behaves as a transcription factor which modulates Fas expression in human cells
AU - Oliveri, Mara
AU - Daga, Antonio
AU - Lunardi, Claudio
AU - Navone, Riccardo
AU - Millo, Romano
AU - Puccetti, Antonio
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - DNase I
KW - Fas
KW - Transcription factor
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U2 - 10.1002/eji.200223817
DO - 10.1002/eji.200223817
M3 - Article
C2 - 14971053
AN - SCOPUS:1642473149
VL - 34
SP - 273
EP - 279
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -