Premium
Regulation of the suppressor of cytokine signaling 3 (SOCS3) by zinc
Author(s) -
Liuzzi Juan,
Tracey Ashley
Publication year - 2012
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.26.1_supplement.lb276
Subject(s) - socs3 , transcription factor , chromatin immunoprecipitation , gene knockdown , zinc finger , biology , gene expression , cancer research , microbiology and biotechnology , promoter , chemistry , signal transduction , gene , stat3 , biochemistry
Zinc is an essential trace element that is known to have anti‐inflammatory activity; however, the mechanisms by which zinc inhibits inflammation are not completely understood. Promoter analysis of the family of suppressors of cytokine signaling (SOCS) revealed that the SOCS3 gene contains four binding sites for the metal regulatory transcription factor 1 (MTF1) located within 1800 bp upstream of the transcription start site. Hence, we hypothesized that zinc regulates the expression of SOCS3 through the activation of the transcription factor MTF1. A series of experiments were carried out with human hepatoma cells (HepG2) to examine the role of zinc and MTF1 in the regulation of SOCS3. We evaluated the effect of zinc excess on the expression of SOCS3 mRNA in cells treated with or without actinomycin D. In addition, we tested the role of MTF1 in the regulation of SOCS3 expression using chromatin immunoprecipitation (ChIP) assay and siRNA. Results indicate that SOCS3 expression is induced by zinc at the transcriptional level. Furthermore, ChIP assay revealed that zinc treatment increases MTF1 binding to the promoter of SOCS3 gene. Lastly, MTF1 knockdown caused a significant reduction of the basal expression of SOCS3. The results suggest that zinc regulates SOCS3 in a MTF1 dependent manner; however, more studies are needed to determine the possible involvement of SOCS3 in the anti‐inflammatory activity of zinc.