Document Detail


Cytochrome P4501A1 promotes G1 phase cell cycle progression by controlling aryl hydrocarbon receptor activity.
MedLine Citation:
PMID:  14742689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Aviva Levine-Fridman; Li Chen; Cornelis J Elferink
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular pharmacology     Volume:  65     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-03-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  461-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cytochrome P-450 CYP1A1 / genetics,  metabolism*
Dose-Response Relationship, Drug
G1 Phase / drug effects,  physiology*
Rats
Receptors, Aryl Hydrocarbon / genetics,  metabolism*
Tetrachlorodibenzodioxin / pharmacology
Grant Support
ID/Acronym/Agency:
ES06676/ES/NIEHS NIH HHS; R01-ES07800/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Aryl Hydrocarbon; 1746-01-6/Tetrachlorodibenzodioxin; EC 1.14.14.1/Cytochrome P-450 CYP1A1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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