PT  - JOURNAL ARTICLE
AU  - Aviva Levine-Fridman
AU  - Li Chen
AU  - Cornelis J. Elferink
TI  - Cytochrome P4501A1 Promotes G<sub>1</sub> Phase Cell Cycle Progression by Controlling Aryl Hydrocarbon Receptor Activity
AID  - 10.1124/mol.65.2.461
DP  - 2004 Feb 01
TA  - Molecular Pharmacology
PG  - 461--469
VI  - 65
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/65/2/461.short
4100  - http://molpharm.aspetjournals.org/content/65/2/461.full
SO  - Mol Pharmacol2004 Feb 01; 65
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 G1 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 G0/G1-to-S phase transition. In contrast, sustained AhR activation in response to TCDD treatment increases p27Kip1 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 p27Kip1 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.