The basic helix-loop-helix/PAS factor Sim is associated with hsp90. Implications for regulation by interaction with partner factors.
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.
Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden.
J
J
McGuire
P
P
Coumailleau
M L
ML
Whitelaw
J A
JA
Gustafsson
L
L
Poellinger
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D001704:Biopolymers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D008024:Ligands; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D001704:Biopolymers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D009687:Nuclear Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; C089449:sim protein, Drosophila