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Inactivation of zinc finger transcription factors provides a mechanism for a gene regulatory role of nitric oxide
Author(s) -
KRöNCKE KLAUSDIETRICH,
CARLBERG CARSTEN
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.1.166
Subject(s) - calcitriol receptor , zinc finger , retinoid x receptor , chemistry , transcription factor , microbiology and biotechnology , transfection , nitric oxide , metallothionein , repressor , zinc , transcription (linguistics) , corepressor , receptor , biophysics , biochemistry , gene , biology , nuclear receptor , linguistics , philosophy , organic chemistry
Nitric oxide (NO) is known to induce Zn 2+ release from the zinc‐storing protein metallothio‐nein and to induce Zn 2+ release within the nuclei and cytoplasm of cells. This suggests that zinc finger proteins may be primary targets of NO‐induced stress. In this study, the specific interaction of the heterodimeric complex of two zinc finger transcription factors, 1α,25‐dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) receptor (VDR) and retinoid × receptor (RXR) with 1α,25(OH) 2 D 3 response elements (VDREs), was used as a model system. NO was applied to this system via the NO donors SNOC and MAMA/NO and caused a dose‐dependent inhibition of VDR‐RXR‐VDRE complex formation (IC 50 values 0.5–0.8 mM). Ligand‐bound or preformed complexes displayed less sensitivity to NO‐induced stress. These in vitro effects of NO were found to be reversible. Functional assays in transiently trans‐fected cells indicated that NO can also act in vivo as a repressor of 1α,25(OH) 2 D 3 signaling (IC 50 value of the slow NO donor DETA/NO, 0.5 mM). These findings suggest that NO has a modulatory role on transcription factors depending on their sensitivity to NO‐induced stress, thus providing a mechanism for a gene regulatory function of NO.—Krõncke, K. D., Carlberg, C. Inactivation of zinc finger transcription factors provides a mechanism for a gene regulatory role of nitric oxide. FASEB J. 13, 166–173 (2000)