Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus

Markus, Steven M.; Taneja, Samir S.; Logan, Susan K.; Li, Wenhui; Ha, Susan; Hittelman, Adam B.; Rogatsky, Inez; Garabedian, Michael J.

doi:10.1091/mbc.01-10-0513

Cited by 80 publications

(95 citation statements)

References 65 publications

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“…This activity might be attributable to UXT alone, although the same report mentioned that this protein was part of a larger complex as observed by velocity gradient sedimentation of HeLa extracts (Markus et al 2002).…”

Section: Uxt (Art-27/stap1)mentioning

confidence: 90%

New insights into the biogenesis of nuclear RNA polymerases?This paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Cloutier

Coulombe

2010

Biochem. Cell Biol.

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More than 30 years of research on nuclear RNA polymerases (RNAP I, II, and III) has uncovered numerous factors that regulate the activity of these enzymes during the transcription reaction. However, very little is known about the machinery that regulates the fate of RNAPs before or after transcription. In particular, the mechanisms of biogenesis of the 3 nuclear RNAPs, which comprise both common and specific subunits, remains mostly uncharacterized and the proteins involved are yet to be discovered. Using protein affinity purification coupled to mass spectrometry (AP-MS), we recently unraveled a high-density interaction network formed by nuclear RNAP subunits from the soluble fraction of human cell extracts. Validation of the dataset using a machine learning approach trained to minimize the rate of false positives and false negatives yielded a highconfidence dataset and uncovered novel interactors that regulate the RNAP II transcription machinery, including a set of proteins we named the RNAP II-associated proteins (RPAPs). One of the RPAPs, RPAP3, is part of an 11-subunit complex we termed the RPAP3/R2TP/prefoldin-like complex. Here, we review the literature on the subunits of this complex, which points to a role in nuclear RNAP biogenesis.

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Section: Uxt (Art-27/stap1)mentioning

confidence: 90%

New insights into the biogenesis of nuclear RNA polymerases?This paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Cloutier

Coulombe

2010

Biochem. Cell Biol.

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“…Generation of Anti-ART-27 Polyclonal Antibodies-Generation of Cterminal anti-ART-27 antibodies has been previously described (24). C-terminal antibodies were affinity-purified by isolation of the IgG fraction on a protein A Sepharose column, followed by affinity purification using Affi-gel 15 resin (Bio-Rad) coupled to the ART-27 peptide immunogen.…”

Section: Methodsmentioning

confidence: 99%

“…ART-27 binds to the AR N terminus and facilitates receptor dependent transcriptional activation. The ART-27 clone was isolated from an androgen-stimulated LNCaP cell cDNA library in a two-hybrid screen designed to identify proteins that interacted with the AR-N terminus (24) and was previously cloned in an exontrapping experiment (25). The ART-27 gene encodes a protein of 157 amino acids with a calculated molecular weight of 18 kDa.…”

mentioning

confidence: 99%

“…The ART-27 gene encodes a protein of 157 amino acids with a calculated molecular weight of 18 kDa. Functional characterization of ART-27 indicates that it is a nuclear protein that interacts with N-terminal rat AR amino acids 153-336, containing AF-1a and a part of AF-1b (24). Biochemical analysis of ART-27 indicates that it interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner.…”

mentioning

confidence: 99%

“…In addition, ART-27 increases the transcriptional potency of AR when overexpressed in a variety of cultured mammalian cells. Mechanistically, ART-27 is likely to function as part of a transcription complex since analysis of ART-27 behavior in density gradient sedimentation of HeLa nuclear cell extracts indicates that it co-sediments as part of a larger complex (24). Although the mechanism by which ART-27 functions as a transcriptional activator is unclear, it is likely that ART-27 acts as an adapter to assemble protein complexes at androgen-responsive promoters.…”

mentioning

confidence: 99%

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ART-27, an Androgen Receptor Coactivator Regulated in Prostate Development and Cancer

Taneja

Swenson

et al. 2004

Journal of Biological Chemistry

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Androgen receptor trapped clone-27 (ART-27) is a newly described transcriptional coactivator that binds to the N terminus of the androgen receptor (AR). Given the vital importance of AR signaling in prostate growth and differentiation, we investigated the role of ART-27 in these processes. Immunohistochemical studies indicate that ART-27 protein is expressed in differentiated epithelial cells of adult human prostate and breast tissue. In prostate, ART-27 is abundant in AR-positive prostate luminal epithelial cells, in contrast to the stroma, where cells express AR but not ART-27. The use of a rat model of androgen depletion/reconstitution indicates that ART-27 expression is associated with the elaboration of differentiated prostate epithelial cells. Interestingly, regulated expression of ART-27 in the androgensensitive LNCaP prostate cancer cell line inhibits androgen-mediated cellular proliferation and enhances androgen-mediated transcription of the prostatespecific antigen (PSA) gene. Consistent with a growth suppressive function, we show that ART-27 expression levels are negligible in human prostate cancer. Importantly, examination of ART-27 protein expression in early fetal prostate development demonstrates that ART-27 is detected only when the developing prostate gland has proceeded from a solid mass of undifferentiated cells to a stage in which differentiated luminal epithelial cells are evident. Thus, ART-27 is an AR cofactor shown to be subject to both cell type and developmental regulation in humans. Overall, the results suggest that decreased levels of ART-27 protein in prostate cancer tissue may occur as a result of de-differentiation, and indicate that ART-27 is likely to regulate a subset of AR-responsive genes important to prostate growth suppression and differentiation.

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Prefoldins

Puerto‐Camacho

2016

Encyclopedia of Life Sciences

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Accurate folding is essential for the proper function of proteins. Prefoldin is one of the chaperoning factors that contribute to protein folding in archaea and eukaryotes. Although it still has maintained its heterohexameric jellyfish‐like structure, it has undergone a progressive diversification throughout evolution, which has ended up with the appearance of the prefoldin‐like complex. This evolutionary change parallels an increasing specificity for substrate recognition, from general binding to unfolded polypeptides in archaea to the highly specific recognition of certain substrates in eukaryotes. Prefoldin action on unfolded polypeptides contributes to its solubilisation in vitro , but acts mainly in vivo as a cochaperone, by transferring nascent polypeptides to class‐II chaperonins. This role of prefoldin is particularly relevant in the assembly of actin filaments and microtubules. In addition to this function, prefoldins also play important roles in the assembly of other multimeric complexes, protein quality control, transcription factors regulation and chromatin dynamics. Key Concepts Prefoldins are heterohexameric jellyfish‐like complexes present in archaea and eukaryotes. Prefoldin acts as a cochaperone and facilitates the supply of unfolded or partially folded substrates to class II chaperonins. Archaeal prefoldin recognises a wide range of unfolded substrates, whereas eukaryotic prefoldin is highly specific. The best‐known role of eukaryotic prefoldin is the cotranslational transfer of nascent actin and tubulin monomers to cytoplasmic class‐II chaperonins for proper folding. Canonical prefoldin also plays functional roles related to gene expression and chromatin dynamics in the nucleus. The prefoldin‐like complex exists only in eukaryotes and is involved in the assembly of multimeric protein complexes, such as nuclear RNA polymerases and phosphatidylinositol‐3‐kinase‐related protein kinases like mTOR.

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Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus

Cited by 80 publications

References 65 publications

ART-27, an Androgen Receptor Coactivator Regulated in Prostate Development and Cancer

Prefoldins

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