UXT
Encyclopedia
Protein UXT also known as androgen receptor trapped clone 27 (ART-27) protein is a protein
that in humans is encoded by the UXT gene
.
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.
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. 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. It also shows homology to prefoldins which are small molecular weight proteins that assemble into molecular chaperone complexes to affect protein folding.
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. More recent studies have more definitively identified ART-27 as a corepressor of AR. 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.
with Androgen receptor
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the UXT gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
UXT interacts with the N-terminus of the androgen receptorAndrogen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
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.
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. 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
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
subunit 5, a pair of prefoldin β-subunits
Prefoldin
Prefoldin is a family of proteins used in protein folding complexes. It is classified as a heterohexameric molecular chaperone in both archaea and eukarya, including humans. A prefoldin molecule works as a transfer protein in conjunction with a molecule of chaperonin to form a chaperone complex...
, and TATA-binding protein-interacting proteins. It also shows homology to prefoldins which are small molecular weight proteins that assemble into molecular chaperone complexes to affect protein folding.
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
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
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. More recent studies have more definitively identified ART-27 as a corepressor of AR. 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
Histone methylation
Histone methylation is the modification of certain amino acids in a histone protein by the addition of one, two, or three methyl groups. In the cell nucleus, DNA is wound around histones...
which otherwise allows for increased transcription of target genes.
Interactions
UXT has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
.