CUTL1

Cut-like homeobox 1
Identifiers
Symbols	CUX1 ; CASP; CDP; CDP/Cut; CDP1; COY1; CUTL1; CUX; Clox; Cux/CDP; GOLIM6; Nbla10317; p100; p110; p200; p75
External IDs	OMIM: 116896 MGI: 88568 HomoloGene: 22551 GeneCards: CUX1 Gene
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding • chromatin binding • protein binding, bridging • sequence-specific DNA binding Cellular component • Golgi membrane • nucleus • cytosol • integral component of Golgi membrane Biological process • negative regulation of transcription from RNA polymerase II promoter • retrograde transport, vesicle recycling within Golgi • kidney development • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • intra-Golgi vesicle-mediated transport • multicellular organismal development • lung development • auditory receptor cell differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of dendrite morphogenesis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1523	13047
Ensembl	ENSG00000257923	ENSMUSG00000029705
UniProt	P39880	P53564
RefSeq (mRNA)	NM_001202543	NM_009986
RefSeq (protein)	NP_001189472	NP_034116
Location (UCSC)	Chr 7: 101.82 – 102.28 Mb	Chr 5: 136.25 – 136.57 Mb
PubMed search

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]

Interactions

Cux1 (CUTL1, CDP, CDP/Cux) has been shown to interact with:

• CREB binding protein,^[8]
• Retinoblastoma protein,^[9] and
• SATB1^[10]

References

1. Scherer SW, Neufeld EJ, Lievens PM, Orkin SH, Kim J, Tsui LC (May 1993). "Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids". Genomics 15 (3): 695–6. doi:10.1006/geno.1993.1130. PMID 8468066.
2. Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A (December 1998). "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. doi:10.1101/gr.8.10.1060. PMC 310788. PMID 9799793.
3. Oka T, Ungar D, Hughson FM, Krieger M (April 2004). "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. doi:10.1091/mbc.E03-09-0699. PMC 404034. PMID 15004235.
4. "Entrez Gene: CUTL1 cut-like 1, CCAAT displacement protein (Drosophila)".
5. Wilson BJ, Harada R, LeDuy L, Hollenberg MD, Nepveu A (January 2009). "CUX1 transcription factor is a downstream effector of the proteinase-activated receptor 2 (PAR2)". J Biol Chem. 284 (1): 36–45. doi:10.1074/jbc.M803808200. PMID 18952606.
6. Press Release (8 December 2013). "Gene promotes one in a hundred of tumours". Wellcome Trust Sanger Institute. Retrieved 17 December 2013.
7. Wong CC, Martincorena I, Rust AG, et al. (2013). "Inactivating CUX1 mutations promote tumorigenesis". Nature Genetics 46 (1): 33–8. doi:10.1038/ng.2846. PMID 24316979.
8. Li S, Aufiero B, Schiltz RL, Walsh MJ (June 2000). "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. doi:10.1073/pnas.130028697. PMC 16517. PMID 10852958.
9. Gupta S, Luong MX, Bleuming SA, Miele A, Luong M, Young D, Knudsen ES, Van Wijnen AJ, Stein JL, Stein GS (September 2003). "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. doi:10.1002/jcp.10335. PMID 12891711.
10. Liu J, Barnett A, Neufeld EJ, Dudley JP (July 1999). "Homeoproteins CDP and SATB1 interact: potential for tissue-specific regulation". Mol. Cell. Biol. 19 (7): 4918–26. doi:10.1128/mcb.19.7.4918. PMC 84297. PMID 10373541.

Further reading

• Ottolenghi S, Mantovani R, Nicolis S, Ronchi A, Giglioni B (1990). "DNA sequences regulating human globin gene transcription in nondeletional hereditary persistence of fetal hemoglobin". Hemoglobin 13 (6): 523–41. doi:10.3109/03630268908993104. PMID 2481658.
• Nepveu A (2001). "Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development". Gene 270 (1–2): 1–15. doi:10.1016/S0378-1119(01)00485-1. PMID 11403998.
• Neufeld EJ, Skalnik DG, Lievens PM, Orkin SH (1993). "Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut". Nat. Genet. 1 (1): 50–5. doi:10.1038/ng0492-50. PMID 1301999.
• 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.
• Chernousov MA, Stahl RC, Carey DJ (1996). "Schwann cells secrete a novel collagen-like adhesive protein that binds N-syndecan". J. Biol. Chem. 271 (23): 13844–53. doi:10.1074/jbc.271.23.13844. PMID 8662884.
• Lievens PM, Tufarelli C, Donady JJ, Stagg A, Neufeld EJ (1997). "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. doi:10.1016/S0378-1119(97)00243-6. PMID 9332351.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (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.
• Chattopadhyay S, Whitehurst CE, Chen J (1998). "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. doi:10.1074/jbc.273.45.29838. PMID 9792700.
• Liu J, Barnett A, Neufeld EJ, Dudley JP (1999). "Homeoproteins CDP and SATB1 Interact: Potential for Tissue-Specific Regulation". Mol. Cell. Biol. 19 (7): 4918–26. doi:10.1128/mcb.19.7.4918. PMC 84297. PMID 10373541.
• Rong Zeng W, Soucie E, Sung Moon N, Martin-Soudant N, Bérubé G, Leduy L, Nepveu A (2000). "Exon/intron structure and alternative transcripts of the CUTL1 gene". Gene 241 (1): 75–85. doi:10.1016/S0378-1119(99)00465-5. PMID 10607901.
• Martin-Soudant N, Drachman JG, Kaushansky K, Nepveu A (2000). "CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes". Leukemia 14 (5): 863–73. doi:10.1038/sj.leu.2401764. PMID 10803519.
• Li S, Aufiero B, Schiltz RL, Walsh MJ (2000). "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. doi:10.1073/pnas.130028697. PMC 16517. PMID 10852958.
• Nirodi C, Hart J, Dhawan P, Moon NS, Nepveu A, Richmond A (2001). "The Role of CDP in the Negative Regulation of CXCL1 Gene Expression". J. Biol. Chem. 276 (28): 26122–31. doi:10.1074/jbc.M102872200. PMC 2665279. PMID 11371564.
• Moon NS, Premdas P, Truscott M, Leduy L, Bérubé G, Nepveu A (2001). "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. doi:10.1128/MCB.21.18.6332-6345.2001. PMC 87367. PMID 11509674.
• Santaguida M, Ding Q, Bérubé G, Truscott M, Whyte P, Nepveu A (2002). "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. doi:10.1074/jbc.M107978200. PMID 11584018.
• Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. doi:10.1074/jbc.M108417200. PMID 11748221.

External links

• CUTL1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.