DNase I behaves as a transcription factor which modulates Fas expression in human cells
Autor: | Antonio Puccetti, Mara Oliveri, Romano Millo, Antonio Daga, Riccardo Navone, Claudio Lunardi |
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Jazyk: | angličtina |
Rok vydání: | 2004 |
Předmět: |
Programmed cell death
media_common.quotation_subject Immunology Cell Apoptosis DNase I Biology Fas ligand Transcription (biology) medicine Deoxyribonuclease I Humans Immunology and Allergy fas Receptor Internalization Transcription factor transcription factor media_common Fas Fas receptor Molecular biology Up-Regulation Cell biology medicine.anatomical_structure Gene Expression Regulation Transcription Factors |
Popis: | 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. |
Databáze: | OpenAIRE |
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