UXT

Protein UXT (Ubiquitously eXpressed Transcript protein) also known as androgen receptor trapped clone 27 (ART-27) protein is a protein that in humans is encoded by the UXT gene.[5][6][7]

UXT
Identifiers
AliasesUXT, ART-27, STAP1, ubiquitously expressed prefoldin like chaperone
External IDsOMIM: 300234 MGI: 1277988 HomoloGene: 40902 GeneCards: UXT
Orthologs
SpeciesHumanMouse
Entrez

8409

22294

Ensembl

ENSG00000126756

ENSMUSG00000001134

UniProt

Q9UBK9

Q9WTZ0

RefSeq (mRNA)

NM_004182
NM_153477

NM_013840

RefSeq (protein)

NP_004173
NP_705582

NP_038868
NP_038868

Location (UCSC)Chr X: 47.65 – 47.66 MbChr X: 20.81 – 20.83 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

UXT interacts with the N-terminus of the androgen receptor and plays a role in facilitating receptor-induced transcriptional activation. It is also likely to be involved in tumorigenesis as it is abundantly expressed in tumor tissues. This gene is part of a gene cluster on chromosome Xp11.23. Alternative splicing results in 2 transcript variants encoding different isoforms.[7]

Transcript variant 2 is 575 bp in length, and it codes for a polypeptide sequence that is 157 amino acids long (~ 18 kDa). It has been shown to interact with two AR N-terminal activation domains that are both required for full transcriptional activation.[8] In addition, it is largely localized to the nucleus and is highly expressed in human prostate epithelial cells as well as breast tissues. ART-27 likely serves to link AR to a larger transcription factor complex as evidenced by its association with a number of proteins including RNA pol II subunit 5, a pair of prefoldin β-subunits, and TATA-binding protein-interacting proteins.[9] It also shows homology to prefoldins which are small molecular weight proteins that assemble into molecular chaperone complexes to affect protein folding.[8]

ART-27 is shown to be subject to both cell type and developmental regulation in humans. Its expression is associated with an abundance of differentiated prostate epithelial cells, and regulated expression in prostate cancer cells results in decreased cell proliferation. Significantly, because decreased levels of ART-27 are consistently found in prostate cancer cells, it likely plays a role in promoting epithelial differentiation via suppression of proliferative pathways.[10] More recent studies have more definitively identified ART-27 as a corepressor of AR.[11] The fact that the increase in gene transcription exhibited upon ART-27 depletion requires the presence of AR implies that it specifically functions as a corepressor of this receptor. Despite the lack of information regarding its mechanisms of suppression, ART-27 likely plays multiple roles that inhibit AR-mediated transcription. In the absence of androgens, ART-27 may bind the AR N terminus and thereby prevent AR-dependent activation of genes involved in cell proliferation. Other mechanisms may include recruitment of ART-27 to AREs or inhibition of histone methylation which otherwise allows for increased transcription of target genes.

Interactions

UXT has been shown to interact with Androgen receptor.[8]

References
  1. GRCh38: Ensembl release 89: ENSG00000126756 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000001134 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Schroer A, Schneider S, Ropers H, Nothwang H (May 1999). "Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue". Genomics. 56 (3): 340–3. doi:10.1006/geno.1998.5712. PMID 10087202.
  6. Zhao H, Wang Q, Zhang H, Liu Q, Du X, Richter M, Greene MI (Nov 2005). "UXT is a novel centrosomal protein essential for cell viability". Mol Biol Cell. 16 (12): 5857–65. doi:10.1091/mbc.E05-08-0705. PMC 1289427. PMID 16221885.
  7. "Entrez Gene: UXT ubiquitously-expressed transcript".
  8. Markus SM, Taneja SS, Logan SK, Li W, Ha S, Hittelman AB, Rogatsky I, Garabedian MJ (February 2002). "Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus". Mol. Biol. Cell. 13 (2): 670–82. doi:10.1091/mbc.01-10-0513. PMC 65658. PMID 11854421.
  9. Nwachukwu JC, Li W, Pineda-Torra I, Huang HY, Ruoff R, Shapiro E, Taneja SS, Logan SK, Garabedian MJ (December 2007). "Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27". Mol. Endocrinol. 21 (12): 2864–76. doi:10.1210/me.2007-0094. PMID 17761951.
  10. Taneja SS, Ha S, Swenson NK, Torra IP, Rome S, Walden PD, Huang HY, Shapiro E, Garabedian MJ, Logan SK (April 2004). "ART-27, an androgen receptor coactivator regulated in prostate development and cancer". J. Biol. Chem. 279 (14): 13944–52. doi:10.1074/jbc.M306576200. PMID 14711828.
  11. Nwachukwu JC, Mita P, Ruoff R, Ha S, Wang Q, Huang SJ, Taneja SS, Brown M, Gerald WL, Garabedian MJ, Logan SK (April 2009). "Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells". Cancer Res. 69 (7): 3140–7. doi:10.1158/0008-5472.CAN-08-3738. PMC 2702238. PMID 19318562.

Further reading
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