Androgen receptor-interacting nuclear proteins

Abstract

In the search for androgen receptor (AR) coregulators, we have recently identified four novel proteins that recognize AR zinc finger region both in vivo and in vitro and activate AR-dependent transcription. One of the proteins is a small nuclear RING finger protein (SNURF) that possesses two interaction interfaces; one for AR and another one for other activators of transcription such as Spl. The second protein is a nuclear Ser/Thr protein kinase (ANPK). This nuclear protein kinase augments specifically AR-dependent transcription, probably through stabilization of receptorcoactivator interactions. The receptor itself does not appear to be a substrate for ANPK. The third protein is dubbed ARIP3-for androgen receptor-interacting protein 3-, and it is a novel member of the so-called PIAS (protein inhibitors for activated STATs) protein family. And finally, the forth protein, termed ARIP4, is a nuclear ATPasc that belongs to the SNFZ-like family. However, it exhibits sequence homology to other

Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland

“…Upon androgen binding, AR regulates the transcription of specific target genes by binding to specific DNA response elements, androgen response elements (AREs), in their promoters. After binding DNA, AR interacts with components of the basal transcription machinery and a variety of general and gene-specific cofactors, resulting in positive or negative effects on gene transcription (Janne et al 2000, Gelmann 2002, Heinlein & Chang 2002. A panel of proteins that can interact with the AR have been identified (ww2.mcgill.ca/androgendb/ARinteract.pdf).…”

Transcriptional ERRγ2-mediated activation is regulated by sentrin-specific proteases

“…Namely PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] proteins promote SUMOylation of transcription factors in a manner that resembles the action of RINGtype ubiquitin E3 ligases [40]. Since PIASxα/ARIP3 (androgen receptor-interacting protein) [41] [42,43] is involved in nuclear receptor regulation we studied the effect of a forced expression on ERRγ regulation. Our data do not support a specific effect (data not shown).…”

“…Mutagenesis of the RF-1 in the context of a GAL4 fusion protein revealed that all mutants proposed to inhibit sumoylation led to a higher activity of the AF-1. Similarly, a Lys 40 to arginine mutant, as well as the mutation of the hydrophobic residue Ile 39 and of the acidic residue Glu 42 to alanine led to higher activity of full-length ERRγ2. Both, superactivation by replacing the potential phosphorylation acceptor Ser 45 with alanine and a phosphorylation-dependent mobility shift of protein DNA complexes during gel electrophoresis speak in favor of a functional PDSM.…”

Stimulation of Prostate Cancer Cellular Proliferation and Invasion by the Androgen Receptor Co-Activator ARA70β

“…[5][6][7] Interestingly, a number of AR co-activators display diverse patterns of expression in prostate cancer. For example, the AR cofactors ARA24, PIAS1, 8 cyclinD1, 9 SRC1, 10 and FHL2 11 appear overexpressed, whereas ARA70 8 and ART-27 12 are reduced in human prostate cancers compared to adjacent benign tissue.…”

“…3,4 An increasing number of AR-interacting proteins have been identified, and several have been shown to function as AR co-activators in cellbased reporter assay. [5][6][7] Interestingly, a number of AR co-activators display diverse patterns of expression in prostate cancer. For example, the AR cofactors ARA24, PIAS1, 8 cyclinD1, 9 SRC1, 10 and FHL2 11 appear overexpressed, whereas ARA70 8 and ART-27 12 are reduced in human prostate cancers compared to adjacent benign tissue.…”