title: TonEBP is inhibited by RNA helicase A via interaction involving the E'F loop.
abstract: TonEBP [TonE (tonicity-responsive enhancer)-binding protein] is a transcriptional activator of the Rel family like NF-kappaB (nuclear factor kappaB) and NFAT (nuclear factor of activated T-cells). TonEBP plays a key role in the protection of cells in the kidney medulla from the deleterious effects of hyperosmolality. This is achieved by enhancing expression of HSP70 (heat-shock protein 70) and other genes whose products drive cellular accumulation of organic osmolytes. TonEBP is stimulated by ambient hypertonicity via multiple pathways that regulate nuclear translocation and transactivation. In the present paper, we report that TonEBP is associated in vivo with RHA (RNA helicase A). The N- and C-termini of RHA bound the E'F loop of the DNA-binding domain of TonEBP. The interaction was not affected by DNA binding or dimerization of TonEBP. Overexpression of RHA inhibited the activity of TonEBP; however, catalytic activity of RHA was dispensable for the inhibition. When the ambient tonicity was raised, the TonEBP-RHA interaction decreased, suggesting that dissociation of RHA is a pathway to stimulate TonEBP. We conclude that the E'F loop of TonEBP interacts with RHA like NFAT and NF-kappaB interact with AP1 (activator protein 1) and the high-mobility group protein HMG-I(Y) respectively. While RHA interacts with and stimulates other transcription factors such as CREB (cAMP-response-element-binding protein), NF-kappaB and mineralocorticoid receptor, it inhibits TonEBP.
authors.affiliation: Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colla
authors.forename: Sang D
authors.initials: SD
authors.lastname: Lee
authors.forename: Mee R
authors.initials: MR
authors.lastname: Sheen
authors.forename: Seung K
authors.initials: SK
authors.lastname: Woo
authors.forename: H Moo
authors.initials: HM
authors.lastname: Kwon
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053487:DEAD-box RNA Helicases; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D011485:Protein Binding; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases