Novel ATPase of SNF2-like protein family interacts with androgen receptor and modulates androgen-dependent transcription.
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.
Rouleau
Nathalie
N
Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki and Helsinki University Central Hospital, Fin-00014 Helsinki, Finland.
Domans'kyi
Andrii
A
Reeben
Mati
M
Moilanen
Anu-Maarit
AM
Havas
Kristina
K
Kang
Zhigang
Z
Owen-Hughes
Tom
T
Palvimo
Jorma J
JJ
Jänne
Olli A
OA
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D007313:Insecta; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics; D000099160:LexA Repressor Protein
D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate; D001426:Bacterial Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases; D014157:Transcription Factors; D001616:beta-Galactosidase; D000099160:LexA Repressor Protein; C499333:SNF2 protein, S cerevisiae