title: ZFC3H1, a zinc finger protein, modulates IL-8 transcription by binding with celastramycin A, a potential immune suppressor.
abstract: 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).
authors.affiliation: Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Ieguchi
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
authors.affiliation: IGBMC, Department of Functional Genomics and Cancer, CNRS/INSERM/Universite de Strasbourg, Strasbourg, France.
authors.forename: Fredric
authors.initials: F
authors.lastname: Coin
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kurata
authors.affiliation: Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maru
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000378:metabolism; D012118:Resorcinols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; D016209:Interleukin-8; D010750:Phosphoproteins; D011758:Pyrroles; D034741:RNA, Small Interfering; D012118:Resorcinols; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000598591:ZFC3H1 protein, human; C472377:celastramycin A; C071447:ERCC1 protein, human; D004720:Endonucleases