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Originally published as MBC in Press, 10.1091/mbc.01-10-0484 on April 3, 2002
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Vol. 13, Issue 6, 2106-2119, June 2002

Novel ATPase of SNF2-like Protein Family Interacts with Androgen Receptor and Modulates Androgen-dependent Transcription

Nathalie Rouleau,* Andrii Domans'kyi,* Mati Reeben,* Anu-Maarit Moilanen,* Kristina Havas,dagger Zhigang Kang,* Tom Owen-Hughes,dagger Jorma J. Palvimo,*Dagger and Olli A. Jänne*§||

 *Biomedicum Helsinki, Institute of Biomedicine,  Dagger Institute of Biotechnology, and  §Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, Fin-00014 Helsinki, Finland; and  dagger Division of Gene Regulation, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland

Nuclear receptors, including the androgen receptor (AR), regulate target cell transcription through interaction with auxiliary proteins to modify chromatin structure. We describe herein a novel AR-interacting protein, termed ARIP4, that has structural features typical of the SNF2-like protein family. With regard to the Snf2 domain, the closest homolog of ARIP4 is the ATRX protein. ARIP4 is a nuclear protein and comprises 1466 amino acids. It interacts with AR in vitro and in cultured yeast and mammalian cells. ARIP4 can be labeled with 8-azido-[gamma -32P]ATP and exhibits DNA-dependent ATPase activity. Like several ATP-dependent chromatin remodeling proteins, ARIP4 generates superhelical torsion within linear DNA fragments in an ATP-dependent manner. With a stably integrated target promoter, ARIP4 elicits a modest enhancement of AR-dependent transactivation. In transient cotransfection assays, ARIP4 modulates AR function in a promoter-dependent manner; it enhances receptor activity on minimal promoters, but does not activate more complex promoters. ARIP4 mutants devoid of ATPase activity fail to alter DNA topology and behave as trans-dominant negative regulators of AR function in transient assays.

|| Corresponding author. E-mail address: olli.janne{at}helsinki.fi.

Molecular Biology of the Cell
Vol. 13, 2106-2119, June 2002
Copyright © 2002 by The American Society for Cell Biology


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