Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein

Cornelis J. Elferink, Nie Lin Ge, Aviva Levine

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) belongs to the basic helix-loop-helix/periodicity/AhR nuclear translocator/simple-minded (Per-Arnt-Sim) family of transcription factors that regulate critical functions during development and tissue homeostasis. Within this family, the AhR is the only member conditionally activated in response to ligand binding, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We recently demonstrated that the AhR interacts with the retinoblastoma protein (pRb). This report presents evidence that a LXCXE motif in the AhR protein confers pRb binding, which is necessary for maximal TCDD induced G1 arrest in rat 5L hepatoma cells. The data support a mechanism whereby pRb seems to regulate G1 cell cycle progression distinct from the direct repression of E2F-mediated transcription. Furthermore, the results indicate that the AhR-pRb interaction regulates TCDD induction of CYP1A1, suggesting that pRb may be a general AhR coactivator.

Original languageEnglish (US)
Pages (from-to)664-673
Number of pages10
JournalMolecular pharmacology
Volume59
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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