A Testis-specific Androgen Receptor Coregulator That Belongs to a Novel Family of Nuclear Proteins

doi:10.1074/jbc.274.6.3700

A Testis-specific Androgen Receptor Coregulator That Belongs to a Novel Family of Nuclear Proteins*

From the ^‡Department of Physiology, Institute of Biomedicine, and the ^¶Department of Clinical Chemistry, University of Helsinki, FIN-00014 Helsinki, Finland and the ^§Departments of Physiology and Pediatrics, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland

Abstract

We have characterized a novel partner for androgen receptor (AR), termed ARIP3, that interacts with the DNA-binding domain/zinc finger region of AR and is predominantly expressed in the testis. Rat ARIP3 is a nuclear protein comprising 572 amino acids. It modulates AR-dependent but not basal transcription, suggesting that ARIP3 acts as an AR transcriptional coregulator. Except for the C-terminal AR-interacting domain, ARIP3 contains distinct regions that are also present in two recently described proteins, a protein inhibitor of activated Stat3 and an RNA helicase II-interacting protein (Gu/RH-II binding protein). Conserved structural features of these proteins indicate the existence of a gene family involved in the regulation of various transcription factors. Collectively, ARIP3 belongs to a novel nuclear protein family and is perhaps the first tissue-specific coregulator of androgen receptor.

Footnotes

↵* This work was supported by grants from the Medical Research Council (Academy of Finland), the Finnish Foundation for Cancer Research, the Jalmari and Rauha Ahokas Foundation, the Research and Science Foundation of Farmos, the Sigrid Jusélius Foundation, Biocentrum Helsinki, the Helsinki University Central Hospital, and the Turku University Central Hospital.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF044058.
↵‖ To whom correspondence should be addressed: Dept. of Physiology, Inst. of Biomedicine, University of Helsinki, P. O. Box 9 (Siltavuorenpenger 20J), FIN-00014 Helsinki, Finland. Tel.: 358-9-1918542; Fax: 358-9-1918681; E-mail:jorma.palvimo{at}helsinki.fi.
↵2 The term “residues” refers always to amino acids.
↵3 A.-M. Moilanen, J. J. Palvimo, and O. A. Jänne, unpublished observations.
↵4 J. J. Palvimo, A.-M. Moilanen, H. Poukka, and O. A. Jänne, unpublished observations.
Abbreviations:

AF

activation function

ANPK

androgen receptor-interacting nuclear protein kinase

AR

androgen receptor

ARE

androgen response element

ARIP

androgen receptor-interacting protein

CMV

cytomegalovirus

DBD

DNA-binding domain

DOTAP

N-[1-(2,3-dioleoyloxy)propyl]N,N,N-trimethylammonium methyl sulfate

GBP

Gu/RH-II binding protein

GST

glutathioneS-transferase

ID

interacting domain

LBD

ligand-binding domain

LUC

luciferase

PCR

polymerase chain reaction

PCAF

p300/CBP-associated factor

PGC

PPAR γ coactivator

PIAS

protein inhibitor of activated STAT

ZFR

zinc finger region

SNURF

small nuclear RING finger

STAT

signal transducer and activator of transcription.
- Received October 5, 1998.
- Revision received November 30, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.