| UXT | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | UXT , ART-27, STAP1, ubiquitously expressed prefoldin like chaperone | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 300234; MGI: 1277988; HomoloGene: 40902; GeneCards: UXT; OMA:UXT - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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 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.
UXT has been shown to interact with Androgen receptor. [8]
The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).
Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene. Often put together with and studied alongside TGFB1I1 is the mouse homologue HIC-5. As the name suggests, TGFB1I1 is an induced form of the larger family of TGFB1. Studies suggest TGFB1I1 plays a role in processes of cell growth, proliferation, migration, differentiation and senescence. TGFB1I1 is most localized at focal adhesion complexes of cells, although it may be found active in the cytosol, nucleus and cell membrane as well.
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the FHL2 gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.
Nuclear receptor coactivator 4, also known as Androgen Receptor Activator (ARA70), is a protein that in humans is encoded by the NCOA4 gene. It plays an important role in ferritinophagy, acting as a cargo receptor, binding to the ferritin heavy chain and latching on to ATG8 on the surface of the autophagosome.
Acyl-CoA-binding protein in humans belongs to the family of Acyl-CoA-binding proteins.
Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.
Lipid phosphate phosphohydrolase 1 also known as phosphatidic acid phosphatase 2a is an enzyme that in humans is encoded by the PPAP2A gene.
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. The TMPRSS2 protein is found in high concentration in the cell membranes of epithelial cells of the lung and of the prostate, but also in the heart, liver and gastrointestinal tract.
E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the RNF14 gene.
Leucine-rich PPR motif-containing protein, mitochondrial is a protein that in humans is encoded by the LRPPRC gene. Transcripts ranging in size from 4.8 to 7.0 kb which result from alternative polyadenylation have been reported for this gene.
Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.
Prefoldin subunit 2 is a protein that in humans is encoded by the PFDN2 gene.
TATA element modulatory factor is a protein that in humans is encoded by the TMF1 gene.
Melanoma-associated antigen 11 is a protein that in humans is encoded by the MAGEA11 gene. It is also involved in the androgen and progesterone receptor signaling pathways.
Tripartite motif-containing protein 68 is a protein that in humans is encoded by the TRIM68 gene.
Proline-rich nuclear receptor coactivator 1 is a protein that, in humans, is encoded by the PNRC1 gene.
Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.
The first antiandrogen was discovered in the 1960s. Antiandrogens antagonise the androgen receptor (AR) and thereby block the biological effects of testosterone and dihydrotestosterone (DHT). Antiandrogens are important for men with hormonally responsive diseases like prostate cancer, benign prostatic hyperplasia (BHP), acne, seborrhea, hirsutism and androgen alopecia. Antiandrogens are mainly used for the treatment of prostate diseases. Research from 2010 suggests that ARs could be linked to the disease progression of triple-negative breast cancer and salivary duct carcinoma and that antiandrogens can potentially be used to treat it.
EPI-001 is the first inhibitor of the androgen receptor amino-terminal domain. The single stereoisomer of EPI-001, EPI-002, is a first-in-class drug that the USAN council assigned a new stem class "-aniten" and the generic name "ralaniten". This distinguishes the anitens novel molecular mechanism from anti androgens that bind the C-terminus ligand-binding domain and have the stem class "lutamide". EPI-001 and its stereoisomers and analogues were discovered by Marianne Sadar and Raymond Andersen, who co-founded the pharmaceutical company ESSA Pharma Inc for the clinical development of anitens for the treatment of castration-resistant prostate cancer (CRPC).
