bcrp - publications

Predict more bcrp - ligand interactions now!


1. J Biol Chem. 2012 Mar 6. [Epub ahead of print]

Intestinal expression of mouse Abcg2/Bcrp gene is under the control of circadian
clock-activating transcription factor-4 pathway.

Hamdan AM, Koyanagi S, Wada E, Kusunose N, Murakami Y, Matsunaga N, Ohdo S.

Max-Plank Institute for Biophysical Chemistry, Germany;

ABCG2, encoding breast cancer resistance protein (BCRP), is a member of
ATP-binding cassette transporters and is often associated with cancer
chemotherapeutic resistance. BCRP is also expressed in a variety of normal cells
and acts as a xenobiotic efflux transporter. Since intestinal BCRP limits
systemic exposure to xenobiotics, alterations in the function and expression of
this transporter could account for part of the variation in oral drug absorption.
In this study, we showed that activating transcription factor-4 (ATF4), a
molecular component of the circadian clock, induced circadian expression of the
Abcg2 gene in the mouse small intestine. Three types of leader exons (termed exon
1A, 1B, and 1C) are identified in the 5'-untranslated region of mouse Abcg2
transcripts. Exon 1B containing Abcg2 transcript was the only isoform detected in
the mouse small intestine, and its mRNA levels oscillated in a circadian
time-dependent manner. ATF4 bound time-dependently to the cAMP response element
within the exon 1B promoter region of the Abcg2 gene, thereby causing the
oscillation of BCRP protein abundance and its efflux pump function. The circadian
clock-ATF4 pathway appears to enhance the function of BCRP during a specific time
window and to modulate intestinal drug absorption. Our findings suggest a
mechanism underlying circadian change in the xenobiotic detoxification.

PMID: 22396548 [PubMed - as supplied by publisher]