CCAR1, a key regulator of mediator complex recruitment to nuclear receptor transcription complexes.

Molecular Cell
Jeong Hoon KimM R Stallcup

Abstract

DNA-bound transcription factors recruit many coactivator proteins to remodel chromatin and activate transcription. The Mediator complex is believed to recruit RNA polymerase II to most protein-encoding genes. It is generally assumed that interaction of Mediator subunits with DNA-binding transcription factors is responsible for Mediator recruitment to promoters. However, we report here that Mediator recruitment by nuclear receptors (NR) requires a coactivator protein, CCAR1 (cell-cycle and apoptosis regulator 1). CCAR1 associates with components of the Mediator and p160 coactivator complexes and is recruited to endogenous NR target genes in response to the appropriate hormone. Reduction of endogenous CCAR1 levels inhibited hormone-induced expression of endogenous NR target genes, hormone-induced recruitment of Mediator components and RNA polymerase II to target gene promoters, and estrogen-dependent growth of breast cancer cells. Thus, CCAR1 regulates expression of key proliferation-inducing genes. CCAR1 also functions as a p53 coactivator, suggesting a broader role in transcriptional regulation.

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Citations

Sep 2, 2011·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·S K BaniwalB Frenkel
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pingping JiangXiaoting Zhang
Aug 13, 2011·Cancer Biotherapy & Radiopharmaceuticals·Xing-Hua LiChai-Ming Zeng
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May 30, 2012·Cell & Bioscience·Jen-Chywan WangCharles A Harris
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Rajas ChodankarMichael R Stallcup
Jan 23, 2015·BioMed Research International·Jessica BrunquellBin Xue
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