The Basic Helix-Loop-Helix/PAS Factor Sim Is Associated with hsp90:
IMPLICATIONS FOR REGULATION BY INTERACTION WITH PARTNER FACTORS (*)
- Jacqueline McGuire(1),
- Pascal Coumailleau(1)(§),
- Murray L. Whitelaw(1)(2),
- Jan-Åke Gustafsson(1) and
- Lorenz Poellinger(1)(¶)
- From the (1)Departments of Medical Nutrition and
- (2)Bioscience, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden
- ¶ To whom correspondence should be addressed. Tel.: 46-8-779-7124; Fax: 46-8-711-6659.
Abstract
Sim is a Drosophila developmental basic helix-loop-helix (bHLH) transcription factor containing a Per-Arnt-Sim (PAS) region of homology. Here we demonstrate that Sim, in analogy to the structurally related bHLH/PAS dioxin receptor, was stably associated with the molecular chaperone hsp90. In the case of the dioxin receptor, release of hsp90 and derepression of receptor function appear to be regulated by ligand binding and dimerization with Arnt, a non-hsp90-associated bHLH/PAS factor. Dimerization with Arnt very efficiently disrupted Sim•hsp90 interaction, a process that required both the bHLH and PAS dimerization motifs of Arnt. Moreover, hsp90 was also released upon dimerization of Sim with the Drosophila PAS factor Per, whereas the hsp90-associated dioxin receptor failed to interact with Sim. These results indicate that hsp90 may play a role in conditional regulation of Sim function, and that Per and possibly bHLH/PAS partner factors may activate Sim by inducing release of hsp90 during the dimerization process.
Footnotes
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↵* This work was supported by the Swedish Cancer Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵(1) The abbreviations and trivial names used are:
- Sim
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single minded
- Per
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period
- bHLH
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basic helix-loop-helix
- PAS
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Per-Arnt-Sim
- hsp90
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90-kDa heat shock protein
- PAGE
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polyacrylamide gel electrophoresis.
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↵(2) J. McGuire, M. L. Whitelaw, L. Tora, and L. Poellinger, unpublished results.
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- Received August 24, 1995.
- Revision received October 20, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
