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| Subject Categories: Chromatin & Transcription | Molecular Biology of Disease |
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| The EMBO Journal
(2006) 25, 2453–2464, doi:10.1038/sj.emboj.7601106 Published online 4 May 2006 |
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| Absence of the steroid receptor coactivator-3 induces B-cell lymphoma |
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| Agnès Coste1, Maria Cristina Antal2, Susan Chan1, Philippe Kastner1, 2, Manuel Mark1, 2, Bert W O'malley3 and Johan Auwerx1, 2 |
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1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, Illkirch, France 2 Institut Clinique de la Souris, Génopole Strasbourg, Illkirch, France 3 Department of Molecular and Cellular Biology, Baylor College of Medecine, Houston, TX, USA To whom correspondence should be addressed Johan Auwerx, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Parc d'Innovation, 1 rue Laurent Fries, BP10142, 67404 Illkirch, France. Tel.: +33 388 653425; Fax: +33 388 653201; E-mail: auwerx@igbmc.u-strasbg.fr Received 24 November 2005; Accepted 29 March 2006; Published online 4 May 2006. |
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| Abstract |
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Steroid receptor coactivator 3 (SRC-3/ACTR/AIB-1/pCIP/RAC3/TRAM-1) is a member of the p160 family of nuclear receptor coactivators that plays an important role in mammary gland growth, development, and tumorigenesis. We show that deletion of SRC-3 gene decreases platelet and increases lymphocytes numbers, leading to the development of malignant B-cell lymphomas upon aging. The expansion of the lymphoid lineage in SRC-3-/- mice is cell autonomous, correlates with an induction of proliferative and antiapoptotic genes secondary to constitutive NF- B activation, and can be reversed by restoration of SRC-3 expression. NF-B activation is explained by the degradation of IB, consequent to increases in free IB kinase, which is no longer inhibited by SRC-3. These results demonstrate that SRC-3 regulates lymphopoiesis and in combination with previous studies indicate that SRC-3 has vastly diverging effects on cell proliferation depending on the cellular context, ranging from proliferative and tumorigenic (breast) to antiproliferative (lymphoid cells) effects. |
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| Keywords: cofactors, hematopoiesis, lymphoma, NF-B, transcription |
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