Biology:CUTL1
 Generic protein structure example |
Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.[1][2][3][4]
Function
The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It regulates gene expression, morphogenesis, and differentiation and it also plays a role in cell cycle progression, particularly at S-phase. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined, and the p200 isoform of Cux1 is processed proteolytically to smaller active isoforms, such as p110.[4] Cux1 DNA binding is stimulated by activation of the PAR2/F2RL1 cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulate Matrix metalloproteinase 10, Interleukin1-alpha, and Cyclo-oxygenase 2 (COX2) genes.[5]
Role in tumor growth
Genetic data from over 7,600 cancer patients shows that over 1% has the deactivated CUX1 which links to progression of tumor growth. Researchers from the Wellcome Trust Sanger Institute reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor, PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other known gene mutations that cause cancer, this deactivated gene is found across many cancer types in this study to be the underlying cause of the disease.[6][7]
CASP
The CUX1 gene Alternatively Spliced Product was first reported in 1997.[9][lower-alpha 1] The CUX1 gene has up to 33 exons. CASP mRNA includes exons 1 through 14 and 25 through 33.[11] The human CASP protein is predicted to contain 678 amino acids, of which 400 are shared with CUTL1.[9] CASP protein is approximately 80 kD.[9] It lacks the DNA binding region of CUTL1,[9][12] but instead contains a trans-membrane domain that allows it to insert into lipid bilayers.[12] It has been localized to the Golgi apparatus.[12]
CASP has been reported to be part of a complex with Golgin 84 that tethers COPI vesicles and is important for retrograde transport in the Golgi and between the Golgi and endoplasmic reticulum.[13] The targeting of vesicles involves tethers and SNAREs.[13]
Interactions
Cux1 (CUTL1, CDP, CDP/Cux) has been shown to interact with:
- CREB binding protein,[14]
- Retinoblastoma protein,[15] and
- SATB1[16]
These physical interactions are reported in BioPlex 2.0
Notes
References
- ↑ "Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids". Genomics 15 (3): 695–6. May 1993. doi:10.1006/geno.1993.1130. PMID 8468066.
- ↑ "Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes". Genome Res. 8 (10): 1060–73. December 1998. doi:10.1101/gr.8.10.1060. PMID 9799793.
- ↑ "The COG and COPI Complexes Interact to Control the Abundance of GEARs, a Subset of Golgi Integral Membrane Proteins". Mol. Biol. Cell 15 (5): 2423–35. April 2004. doi:10.1091/mbc.E03-09-0699. PMID 15004235.
- ↑ 4.0 4.1 "Entrez Gene: CUTL1 cut-like 1, CCAAT displacement protein (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1523.
- ↑ "CUX1 transcription factor is a downstream effector of the proteinase-activated receptor 2 (PAR2)". J. Biol. Chem. 284 (1): 36–45. January 2009. doi:10.1074/jbc.M803808200. PMID 18952606.
- ↑ Press Release (8 December 2013). "Gene promotes one in a hundred of tumours". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/about/press/2013/131208.html.
- ↑ "Inactivating CUX1 mutations promote tumorigenesis". Nature Genetics 46 (1): 33–8. 2013. doi:10.1038/ng.2846. PMID 24316979.
- ↑ "Interaction of Golgin-84 with the COG complex mediates the intra-Golgi retrograde transport". Traffic 11 (12): 1552–66. 2010. doi:10.1111/j.1600-0854.2010.01123.x. PMID 20874812.
- ↑ 9.0 9.1 9.2 9.3 "CASP, a novel, highly conserved alternative-splicing product of the CDP/cut/cux gene, lacks cut-repeat and homeo DNA-binding domains, and interacts with full-length CDP in vitro". Gene 197 (1–2): 73–81. 1997. doi:10.1016/s0378-1119(97)00243-6. PMID 9332351.
- ↑ "The N-terminal coiled coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with the scaffolding protein CASP". The Journal of Biological Chemistry 277 (35): 32302–9. 2002. doi:10.1074/jbc.M202898200. PMID 12052827.
- ↑ "CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers". Nature Reviews Cancer 14 (10): 673–82. 2014. doi:10.1038/nrc3805. PMID 25190083. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=145247.
- ↑ 12.0 12.1 12.2 "CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin". Molecular Biology of the Cell 13 (11): 3761–74. 2002. doi:10.1091/mbc.E02-06-0349. PMID 12429822.
- ↑ 13.0 13.1 "Golgin tethers define subpopulations of COPI vesicles". Science 307 (5712): 1095–8. 2005. doi:10.1126/science.1108061. PMID 15718469. Bibcode: 2005Sci...307.1095M.
- ↑ "Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7166–71. June 2000. doi:10.1073/pnas.130028697. PMID 10852958. Bibcode: 2000PNAS...97.7166L.
- ↑ "Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription". J. Cell. Physiol. 196 (3): 541–56. September 2003. doi:10.1002/jcp.10335. PMID 12891711.
- ↑ "Homeoproteins CDP and SATB1 interact: potential for tissue-specific regulation". Mol. Cell. Biol. 19 (7): 4918–26. July 1999. doi:10.1128/mcb.19.7.4918. PMID 10373541.
Further reading
- "DNA sequences regulating human globin gene transcription in nondeletional hereditary persistence of fetal hemoglobin". Hemoglobin 13 (6): 523–41. 1990. doi:10.3109/03630268908993104. PMID 2481658.
- "Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development". Gene 270 (1–2): 1–15. 2001. doi:10.1016/S0378-1119(01)00485-1. PMID 11403998.
- "Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut". Nat. Genet. 1 (1): 50–5. 1993. doi:10.1038/ng0492-50. PMID 1301999.
- "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.
- "Schwann cells secrete a novel collagen-like adhesive protein that binds N-syndecan". J. Biol. Chem. 271 (23): 13844–53. 1996. doi:10.1074/jbc.271.23.13844. PMID 8662884.
- "CASP, a novel, highly conserved alternative-splicing product of the CDP/cut/cux gene, lacks cut-repeat and homeo DNA-binding domains, and interacts with full-length CDP in vitro". Gene 197 (1–2): 73–81. 1997. doi:10.1016/S0378-1119(97)00243-6. PMID 9332351.
- "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.
- "A nuclear matrix attachment region upstream of the T cell receptor beta gene enhancer binds Cux/CDP and SATB1 and modulates enhancer-dependent reporter gene expression but not endogenous gene expression". J. Biol. Chem. 273 (45): 29838–46. 1998. doi:10.1074/jbc.273.45.29838. PMID 9792700.
- "Homeoproteins CDP and SATB1 Interact: Potential for Tissue-Specific Regulation". Mol. Cell. Biol. 19 (7): 4918–26. 1999. doi:10.1128/mcb.19.7.4918. PMID 10373541.
- "Exon/intron structure and alternative transcripts of the CUTL1 gene". Gene 241 (1): 75–85. 2000. doi:10.1016/S0378-1119(99)00465-5. PMID 10607901.
- "CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes". Leukemia 14 (5): 863–73. 2000. doi:10.1038/sj.leu.2401764. PMID 10803519.
- "Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7166–71. 2000. doi:10.1073/pnas.130028697. PMID 10852958. Bibcode: 2000PNAS...97.7166L.
- "The Role of CDP in the Negative Regulation of CXCL1 Gene Expression". J. Biol. Chem. 276 (28): 26122–31. 2001. doi:10.1074/jbc.M102872200. PMID 11371564.
- "S Phase-Specific Proteolytic Cleavage Is Required To Activate Stable DNA Binding by the CDP/Cut Homeodomain Protein". Mol. Cell. Biol. 21 (18): 6332–45. 2001. doi:10.1128/MCB.21.18.6332-6345.2001. PMID 11509674.
- "Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2)". J. Biol. Chem. 276 (49): 45780–90. 2002. doi:10.1074/jbc.M107978200. PMID 11584018.
- "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. 2002. doi:10.1074/jbc.M108417200. PMID 11748221. https://digital.csic.es/bitstream/10261/112516/4/jbc.M108417200.full.pdf.
External links
- CUTL1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human CUX1 genome location and CUX1 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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