Reference - Detail
|Author||Tomita T, Ieguchi K, Coin F, Kato Y, Kikuchi H, Oshima Y, Kurata S, Maru Y.|
|Title||ZFC3H1, a zinc finger protein, modulates IL-8 transcription by binding with celastramycin A, a potential immune suppressor.|
Celastramycin A, a small molecule that inhibits the production of antibacterial peptides in an ex vivo culture system of Drosophila, suppresses the TNFα-mediated induction of IL-8 in mammalian cells. To understand its molecular mechanism, we examined Celastramycin A binding proteins and investigated their biological functions. Our screening and subsequent pull-down assay revealed ZFC3H1 (also known as CCDC131 or CSRC2), an uncharacterized zinc finger protein, as a Celastramycin A binding protein. The knockdown of ZFC3H1 reduced IL-8 expression levels in the TNFα-stimulated lung carcinoma cell line, LU99, and UV-irradiated HeLa cells. Based on reporter assay results, we concluded that ZFC3H1 participates in the transcriptional activation of IL-8. The findings of our UV-irradiation experiments implied that ZFC3H1 may indirectly interact with ERCC1 in an activated DNA repair complex. Thus, we designated ZFC3H1 as a mammalian target of Celastramycin A (mTOC).
|MeSH||Cell Line, Tumor DNA-Binding Proteins / metabolism Endonucleases / metabolism Gene Expression / drug effects Gene Expression / radiation effects HeLa Cells Humans Interleukin-8 / genetics Interleukin-8 / metabolism* Phosphoproteins / antagonists & inhibitors Phosphoproteins / genetics Phosphoproteins / metabolism* Protein Binding Pyrroles / chemistry Pyrroles / metabolism Pyrroles / pharmacology* RNA Interference RNA Stability RNA, Small Interfering / metabolism Resorcinols / chemistry Resorcinols / metabolism Resorcinols / pharmacology* Signal Transduction / drug effects Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism* Transcriptional Activation / drug effects Tumor Necrosis Factor-alpha / pharmacology Ultraviolet Rays|
|WOS Category||CELL BIOLOGY|
|Human and Animal Cells||Lu99(RCB1900)|