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REGULATION OF NUCLEAR TRANSLOCATION OF HDAC3 BY IKBa IS REQUIRED FOR TNF‐INHIBITION OF PPARg FUNCTION
Author(s) -
Gao Zhanguo,
Ye Jianping
Publication year - 2006
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.20.4.a525-c
Subject(s) - hdac3 , chromosomal translocation , tumor necrosis factor alpha , microbiology and biotechnology , nucleus , cytoplasm , chemistry , biology , biochemistry , gene , endocrinology , histone deacetylase , histone
Inhibition of PPARγ function by TNF‐α contributes to metabolic disorder in glucose and fatty acids under inflammation and cancer, but the molecular mechanism remains to be fully understood. In this study, we demonstrate that nuclear translocation of HDAC3 is regulated by TNF‐α, and this event is required for inhibition of the transcriptional activity of PPARγ by TNF‐α. HDAC3 is associated with IkBα in the cytoplasm. After IkBα degradation in response to TNF‐α, HDAC3 is subject to nuclear translocation leading to an increase in HDAC3 activity in the nucleus. This mechanism determines subcellular distribution of HDAC3. Knockout of IkBα, but not p65 or p50, leads to disappearance of HDAC3 in the cytoplasm. This is associated with HDAC3 enrichment in the nucleus. The inhibition of PPARγ by TNF‐α happens without a reduction in the DNA‐binding activity of PPARγ . These results support that IkBα‐dependent nuclear translocation of HDAC3 is responsible for PPARγ inhibition by TNF‐α.