57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation.

May 11, 2006International journal of molecular medicine

The 57Arg part of DEC2 protein is essential for blocking CLOCK/BMAL2-driven gene activation

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Abstract

Substituting arginine 57 in DEC2 diminishes its suppressive activity on CLOCK/BMAL2-mediated transactivation.

  • The basic helix-loop-helix transcription factors DEC2 and DEC1 are crucial for regulating circadian rhythms in the suprachiasmatic nucleus.
  • Mammalian circadian rhythms are governed by molecular systems that involve a negative-feedback loop.
  • CLOCK/BMAL1 and CLOCK/BMAL2 enhance DEC2 transcription through specific DNA sequences known as CACGTG E-boxes.
  • Substituting arginine 57 for alanine or lysine in DEC2 reduces its ability to suppress CLOCK/BMAL2-mediated transactivation.
  • Substituting proline 48 for alanine in DEC2 does not affect its suppressive activity.
  • DEC2 and its substitution mutants are expressed at nearly the same levels, indicating that changes in activity are not due to differences in protein expression.

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