The FBP interacting repressor targets TFIIH to inhibit activated transcription

J Liu1, L He, I Collins

  • 1Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.

Molecular Cell
|July 6, 2000
PubMed

Insights

A novel FBP interacting repressor (FIR) protein binds FUSE-binding protein (FBP) and blocks c-myc transcription. FIR selectively inhibits TFIIH

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Transcription Factors

Background:

  • FUSE-binding protein (FBP) is crucial for c-myc gene expression.
  • FBP binds the far upstream element (FUSE) of active c-myc genes.
  • FBP possesses both transcription activation and repression capabilities.

Purpose of the Study:

  • To identify novel proteins interacting with FBP.
  • To investigate the role of FBP-interacting proteins in c-myc transcription regulation.
  • To elucidate the mechanism by which FBP interacting repressor (FIR) modulates transcription.

Main Methods:

  • Co-immunoprecipitation to identify interacting proteins.
  • Reporter gene assays to measure c-myc promoter activity.
  • In vitro transcription assays using purified transcription factors.
  • Site-directed mutagenesis to map functional domains.

Main Results:

  • A novel 60 kDa protein, FBP interacting repressor (FIR), was identified.
  • FIR binds to FBP via its nucleic acid-binding domain, forming a ternary complex with FUSE.
  • FIR represses activator-dependent, but not basal, transcription through TFIIH.
  • The N-terminus of FIR contains an activator-selective repression domain that targets TFIIH's p89/XPB helicase.

Conclusions:

  • FIR acts as a repressor of c-myc transcription by interfering with TFIIH.
  • FIR locks TFIIH in an activation-resistant state while allowing basal transcription.
  • FIR provides a novel mechanism for regulating gene expression through targeted inhibition of transcription machinery.

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