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

Cornelis Elferink, Nie Lin Ge, Aviva Levine

Research output: Contribution to journalArticle

100 Citations (Scopus)

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
StatePublished - 2001
Externally publishedYes

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Aryl Hydrocarbon Receptors
Retinoblastoma Protein
Aryl Hydrocarbon Receptor Nuclear Translocator
Cytochrome P-450 CYP1A1
Periodicity
Hepatocellular Carcinoma
Cell Cycle
Homeostasis
Transcription Factors
Ligands
Polychlorinated Dibenzodioxins
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein. / Elferink, Cornelis; Ge, Nie Lin; Levine, Aviva.

In: Molecular Pharmacology, Vol. 59, No. 4, 2001, p. 664-673.

Research output: Contribution to journalArticle

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