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All‐trans retinoic acid prevents KLF4 deacetylation through inducing dissociation of KLF4 with HDAC2 in vascular smooth muscle cells
Author(s) -
Meng Fang,
Han Mei,
Zheng Bin,
Wen Jinkun
Publication year - 2009
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.23.1_supplement.lb187
Subject(s) - histone deacetylase 2 , klf4 , acetylation , phosphorylation , western blot , chemistry , histone deacetylase , histone , histone deacetylase 5 , biochemistry , microbiology and biotechnology , cancer research , biology , transcription factor , gene , sox2
We previously showed that KLF4 is required for the expression of VSMC differentiation marker genes induced by ATRA. Histone deacetylase 2 (HDAC2) interacts with KLF4 and regulates its acetylation and transcriptional activity. In this report, we show that KLF4 acetylation is regulated by its interaction with HDAC2 in ATRA‐induced VSMCs. To determine whether ATRA affects KLF4 modifications, the phosphorylation and acetylation of KLF4, which regulate KLF4 functions, were analyzed. Immunoprecipitation assay showed that level of phosphorylated KLF4 markedly increased in VSMCs treated with 10 µmol/L of ATRA . Similarly, KLF4 acetylation level was also significantly enhanced after VSMCs were treated with ATRA. To investigate the mechanism by which ATRA stimulates KLF4 acetylation, the interaction of KLF4 in vitro and in vivo with HDAC2, which is highly expression in ATRA‐treated VSMCs, was detected by cross‐CoIP and GST pull‐down. Western blot analysis showed that association of HDAC2 with KLF4 decreased in a time‐dependent manner after ATRA stimulation. Meanwhile, the increase in HDAC2 phosphorylation was observed in VSMCs treated with ATRA . These results suggest that ATRA increases KLF4 acetylation via inhibiting its interaction with HDAC2 and suppressing KLF4 deacetylation by HDAC2 in VSMCs. Furthermore, we showed for the first time that JNK mediates ATRA‐induced HDAC2 phosphorylation.