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.[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
- ^ 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1289427.
- ^ a b "Entrez Gene: UXT ubiquitously-expressed transcript". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8409.
- ^ a b c 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=65658.
- ^ 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.
- ^ 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2702238.
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Zhang QH, Ye M, Wu XY, et al. (2001). "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. doi:10.1101/gr.140200. PMC 310934. PMID 11042152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310934.
- Weinmann AS, Yan PS, Oberley MJ, et al. (2002). "Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis". Genes Dev. 16 (2): 235–44. doi:10.1101/gad.943102. PMC 155318. PMID 11799066. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=155318.
- Liu L, McKeehan WL (2002). "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. doi:10.1006/geno.2001.6679. PMID 11827465.
- Thiselton DL, McDowall J, Brandau O, et al. (2002). "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. doi:10.1006/geno.2002.6733. PMID 11944989.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Liu L, Amy V, Liu G, McKeehan WL (2003). "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. doi:10.1290/1543-706X(2002)38<582:NCIMAT>2.0.CO;2. PMID 12762840.
- Gstaiger M, Luke B, Hess D, et al. (2003). "Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI". Science 302 (5648): 1208–12. doi:10.1126/science.1088401. PMID 14615539.
- Rayala HJ, Kendirgi F, Barry DM, et al. (2004). "The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155". Mol. Cell Proteomics 3 (2): 145–55. doi:10.1074/mcp.M300106-MCP200. PMID 14645504.
- Lehner B, Sanderson CM (2004). "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442147.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome". Nature 434 (7031): 325–37. doi:10.1038/nature03440. PMC 2665286. PMID 15772651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2665286.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- Moss TN, Vo A, McKeehan WL, Liu L (2007). "UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation". In Vitro Cell. Dev. Biol. Anim. 43 (3–4): 139–46. doi:10.1007/s11626-007-9016-6. PMID 17554592.
- Sun S, Tang Y, Lou X, et al. (2007). "UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome". J. Cell Biol. 178 (2): 231–44. doi:10.1083/jcb.200611081. PMC 2064443. PMID 17620405. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2064443.