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Mol Cell Endocrinol. 2014 Aug 25;394(1-2):47-58. doi: 10.1016/j.mce.2014.06.021. Epub 2014 Jul 6.

A steroid receptor coactivator acts as the DNA-binding partner of the methoprene-tolerant protein in regulating juvenile hormone response genes.

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Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA. Electronic address:


Methoprene-tolerant (Met) protein is a juvenile hormone (JH) receptor in insects. JH-bound Met forms a complex with the βFtz-F1-interacting steroid receptor coactivator (FISC) and together they regulate JH response genes in mosquitoes. Both proteins contain basic helix-loop-helix (bHLH) and PAS motifs. Here we demonstrated that FISC is the obligatory partner of Met for binding to JH-response elements (JHREs). Met or FISC alone could not bind a previously characterized JHRE, while formation of the Met-FISC complex was necessary and sufficient to bind to the JHRE. This binding required participation of the DNA-binding domains of both Met and FISC. The optimal DNA sequence recognized by Met and FISC contained a core consensus sequence GCACGTG. While formation of the Met-FISC complex in mosquito cells was induced by JH, heterodimerization and DNA binding of bacterially expressed Met and FISC were JH-independent, implying that additional mosquito proteins were required to modulate formation of the receptor complex.


Helix–loop–helix transcription factors; Hormone receptor; Hormone response element; Insects; Protein–protein interaction; Transcription regulation

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