Biochem Pharmacol 2007,
PMID: 17559812
Matsuoka, Hideaki; Fujimura, Takao; Hayashi, Masako; Matsuda, Kaori; Ishii, Yoshinori; Aramori, Ichiro; Mutoh, Seitaro
Previous studies have shown that HDAC inhibitors selectively inhibit IL-2 gene expression, but the mechanism of this inhibition remains to be elucidated. It was recently reported that HDAC4, a component of the nuclear hormone receptor corepressor (N-CoR) complex, associates with the IL-2 promoter via the transcription factor myocyte enhancer factor 2 (MEF2). We therefore focused on the role of HDAC4/N-CoR complex in the transcriptional regulation of IL-2. Four approaches were used to characterize this role and to investigate the relation between the regulatory function of HDAC4/N-CoR complex and HDAC4-enzymatic activity: (i) HDAC4 silencing by RNA interference, (ii) overexpression of N-CoR repression domain 3 (RD3), (iii) overexpression of HDAC4 point mutants, and (iv) treatment with HDAC inhibitors. Here, we report that HDAC4 plays an essential role in IL-2 promoter activation, and that the formation of the HDAC4/N-CoR complex, which is closely related to HDAC4-enzymatic activity, might be involved in HDAC inhibitor-mediated inhibition of IL-2 gene expression. These observations indicate that the selective inhibition of HDAC4 or the interaction of HDAC4 with N-CoR is likely a potential target for the development of novel immunosuppressants.
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Text Mining Data
IL-2 → HDAC4/N-CoR complex: "
Disruption of
HDAC4/N-CoR complex by histone deacetylase inhibitors
leads to inhibition of
IL-2 gene expression
"
IL-2 → HDAC4/N-CoR: "
Disruption of HDAC4/N-CoR complex by histone deacetylase inhibitors leads to inhibition of IL-2 gene expression
"
IL-2 → HDAC: "
Previous studies have shown that HDAC inhibitors selectively inhibit IL-2 gene expression, but the mechanism of this inhibition remains to be elucidated
"
IL-2 ⊣ HDAC4/N-CoR complex: "
We therefore focused on the role of HDAC4/N-CoR complex in the transcriptional regulation of IL-2
"
IL-2 ⊣ HDAC4/N-CoR: "
We therefore focused on the role of HDAC4/N-CoR complex in the transcriptional regulation of IL-2
"
IL-2 — HDAC4: "
Here, we report that HDAC4 plays an essential role in IL-2 promoter activation, and that the formation of the HDAC4/N-CoR complex, which is closely related to HDAC4-enzymatic activity, might be involved in HDAC inhibitor mediated inhibition of IL-2 gene expression
"
Manually curated Databases
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