Biology:UXT
Generic protein structure example |
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.[1][2][3]
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.[3]
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.[4] 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.[5] It also shows homology to prefoldins which are small molecular weight proteins that assemble into molecular chaperone complexes to affect protein folding.[4]
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.[6] More recent studies have more definitively identified ART-27 as a corepressor of AR.[7] 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.[4]
References
- ↑ "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. May 1999. doi:10.1006/geno.1998.5712. PMID 10087202.
- ↑ "UXT is a novel centrosomal protein essential for cell viability". Mol Biol Cell 16 (12): 5857–65. Nov 2005. doi:10.1091/mbc.E05-08-0705. PMID 16221885.
- ↑ 3.0 3.1 "Entrez Gene: UXT ubiquitously-expressed transcript". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8409.
- ↑ 4.0 4.1 4.2 "Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus". Mol. Biol. Cell 13 (2): 670–82. February 2002. doi:10.1091/mbc.01-10-0513. PMID 11854421.
- ↑ "Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27". Mol. Endocrinol. 21 (12): 2864–76. December 2007. doi:10.1210/me.2007-0094. PMID 17761951.
- ↑ "ART-27, an androgen receptor coactivator regulated in prostate development and cancer". J. Biol. Chem. 279 (14): 13944–52. April 2004. doi:10.1074/jbc.M306576200. PMID 14711828.
- ↑ "Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells". Cancer Res. 69 (7): 3140–7. April 2009. doi:10.1158/0008-5472.CAN-08-3738. PMID 19318562.
Further reading
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. 2001. doi:10.1101/gr.140200. PMID 11042152.
- "Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis". Genes Dev. 16 (2): 235–44. 2002. doi:10.1101/gad.943102. PMID 11799066.
- "Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity". Genomics 79 (1): 124–36. 2002. doi:10.1006/geno.2001.6679. PMID 11827465.
- "An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders". Genomics 79 (4): 560–72. 2002. doi:10.1006/geno.2002.6733. PMID 11944989.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells". In Vitro Cell. Dev. Biol. Anim. 38 (10): 582–94. 2003. doi:10.1290/1543-706X(2002)38<582:NCIMAT>2.0.CO;2. PMID 12762840.
- "Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI". Science 302 (5648): 1208–12. 2003. doi:10.1126/science.1088401. PMID 14615539. Bibcode: 2003Sci...302.1208G.
- "The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155". Mol. Cell. Proteomics 3 (2): 145–55. 2004. doi:10.1074/mcp.M300106-MCP200. PMID 14645504.
- "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–23. 2004. doi:10.1101/gr.2122004. PMID 15231747.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "The DNA sequence of the human X chromosome". Nature 434 (7031): 325–37. 2005. doi:10.1038/nature03440. PMID 15772651. Bibcode: 2005Natur.434..325R.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation". In Vitro Cell. Dev. Biol. Anim. 43 (3–4): 139–46. 2007. doi:10.1007/s11626-007-9016-6. PMID 17554592.
- "UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome". J. Cell Biol. 178 (2): 231–44. 2007. doi:10.1083/jcb.200611081. PMID 17620405.