TonEBP [TonE (tonicity-responsive enhancer)-binding protein] is a transcriptional activator of the Rel family like NF-κB (nuclear factor κB) 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-κB 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-κB and mineralocorticoid receptor, it inhibits TonEBP.
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January 2006
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Research Article|
December 12 2005
TonEBP is inhibited by RNA helicase A via interaction involving the E′F loop
Emanuela Colla;
Emanuela Colla
1Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, U.S.A.
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Sang D. Lee;
Sang D. Lee
1
1Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, U.S.A.
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Mee R. Sheen;
Mee R. Sheen
1Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, U.S.A.
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Seung K. Woo;
Seung K. Woo
1Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, U.S.A.
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H. Moo Kwon
H. Moo Kwon
2
1Department of Medicine, University of Maryland, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, U.S.A.
2To whom correspondence should be addressed (email mkwon@medicine.umaryland.edu).
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Biochem J (2006) 393 (1): 411–419.
Article history
Received:
July 05 2005
Revision Received:
September 07 2005
Accepted:
September 21 2005
Accepted Manuscript online:
September 21 2005
Citation
Emanuela Colla, Sang D. Lee, Mee R. Sheen, Seung K. Woo, H. Moo Kwon; TonEBP is inhibited by RNA helicase A via interaction involving the E′F loop. Biochem J 1 January 2006; 393 (1): 411–419. doi: https://doi.org/10.1042/BJ20051082
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