Cytochrome P4501A1 Promotes G1 Phase Cell Cycle Progression by Controlling Aryl Hydrocarbon Receptor Activity

Aviva Levine-Fridman, Li Chen, Cornelis Elferink

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The aryl hydrocarbon receptor (AhR) transcription factor is increasingly recognized as functioning in cell cycle control. Several recent reports have shown that AhR activity in the absence of exogenous agonists or presence of the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin can affect G 1 phase progression in cultured cells. Serum release of serum-starved (G0) 5L rat hepatoma cells triggers transient AhR activation and P4501A1 protein expression concomitant with the G 0/G1-to-S phase transition. In contrast, sustained AhR activation in response to TCDD treatment increases p27Kip expression in addition to P4501A1, resulting in G1 phase cell cycle arrest. Treating serum-released 5L cells with the alkyne metabolism-based P4501A1 inhibitor 1-(1-propynyl)pyrene results in prolonged AhR activation, enhanced p27Kip expression, and G1 phase arrest after serum release. The data are consistent with a cell cycle role for P4501A1 because they show that P4501A1 negatively regulates the duration of AhR action through the metabolic removal of the receptor agonist, thereby preventing AhR-mediated G1 phase arrest.

Original languageEnglish (US)
Pages (from-to)461-469
Number of pages9
JournalMolecular Pharmacology
Volume65
Issue number2
DOIs
StatePublished - Feb 2004

Fingerprint

Aryl Hydrocarbon Receptors
G1 Phase
Cytochromes
Cell Cycle
Serum
G1 Phase Cell Cycle Checkpoints
Alkynes
Phase Transition
Cell Cycle Checkpoints
S Phase
Hepatocellular Carcinoma
Cultured Cells
Transcription Factors
Ligands

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cytochrome P4501A1 Promotes G1 Phase Cell Cycle Progression by Controlling Aryl Hydrocarbon Receptor Activity. / Levine-Fridman, Aviva; Chen, Li; Elferink, Cornelis.

In: Molecular Pharmacology, Vol. 65, No. 2, 02.2004, p. 461-469.

Research output: Contribution to journalArticle

@article{8056622f6a3c4a40b49d2adf60cb8c2b,
title = "Cytochrome P4501A1 Promotes G1 Phase Cell Cycle Progression by Controlling Aryl Hydrocarbon Receptor Activity",
abstract = "The aryl hydrocarbon receptor (AhR) transcription factor is increasingly recognized as functioning in cell cycle control. Several recent reports have shown that AhR activity in the absence of exogenous agonists or presence of the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin can affect G 1 phase progression in cultured cells. Serum release of serum-starved (G0) 5L rat hepatoma cells triggers transient AhR activation and P4501A1 protein expression concomitant with the G 0/G1-to-S phase transition. In contrast, sustained AhR activation in response to TCDD treatment increases p27Kip expression in addition to P4501A1, resulting in G1 phase cell cycle arrest. Treating serum-released 5L cells with the alkyne metabolism-based P4501A1 inhibitor 1-(1-propynyl)pyrene results in prolonged AhR activation, enhanced p27Kip expression, and G1 phase arrest after serum release. The data are consistent with a cell cycle role for P4501A1 because they show that P4501A1 negatively regulates the duration of AhR action through the metabolic removal of the receptor agonist, thereby preventing AhR-mediated G1 phase arrest.",
author = "Aviva Levine-Fridman and Li Chen and Cornelis Elferink",
year = "2004",
month = "2",
doi = "10.1124/mol.65.2.461",
language = "English (US)",
volume = "65",
pages = "461--469",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Cytochrome P4501A1 Promotes G1 Phase Cell Cycle Progression by Controlling Aryl Hydrocarbon Receptor Activity

AU - Levine-Fridman, Aviva

AU - Chen, Li

AU - Elferink, Cornelis

PY - 2004/2

Y1 - 2004/2

N2 - The aryl hydrocarbon receptor (AhR) transcription factor is increasingly recognized as functioning in cell cycle control. Several recent reports have shown that AhR activity in the absence of exogenous agonists or presence of the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin can affect G 1 phase progression in cultured cells. Serum release of serum-starved (G0) 5L rat hepatoma cells triggers transient AhR activation and P4501A1 protein expression concomitant with the G 0/G1-to-S phase transition. In contrast, sustained AhR activation in response to TCDD treatment increases p27Kip expression in addition to P4501A1, resulting in G1 phase cell cycle arrest. Treating serum-released 5L cells with the alkyne metabolism-based P4501A1 inhibitor 1-(1-propynyl)pyrene results in prolonged AhR activation, enhanced p27Kip expression, and G1 phase arrest after serum release. The data are consistent with a cell cycle role for P4501A1 because they show that P4501A1 negatively regulates the duration of AhR action through the metabolic removal of the receptor agonist, thereby preventing AhR-mediated G1 phase arrest.

AB - The aryl hydrocarbon receptor (AhR) transcription factor is increasingly recognized as functioning in cell cycle control. Several recent reports have shown that AhR activity in the absence of exogenous agonists or presence of the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin can affect G 1 phase progression in cultured cells. Serum release of serum-starved (G0) 5L rat hepatoma cells triggers transient AhR activation and P4501A1 protein expression concomitant with the G 0/G1-to-S phase transition. In contrast, sustained AhR activation in response to TCDD treatment increases p27Kip expression in addition to P4501A1, resulting in G1 phase cell cycle arrest. Treating serum-released 5L cells with the alkyne metabolism-based P4501A1 inhibitor 1-(1-propynyl)pyrene results in prolonged AhR activation, enhanced p27Kip expression, and G1 phase arrest after serum release. The data are consistent with a cell cycle role for P4501A1 because they show that P4501A1 negatively regulates the duration of AhR action through the metabolic removal of the receptor agonist, thereby preventing AhR-mediated G1 phase arrest.

UR - http://www.scopus.com/inward/record.url?scp=1642579495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642579495&partnerID=8YFLogxK

U2 - 10.1124/mol.65.2.461

DO - 10.1124/mol.65.2.461

M3 - Article

VL - 65

SP - 461

EP - 469

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 2

ER -