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.[6] Cux1 DNA binding is stimulated by activation of thePAR2/F2RL1 cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulateMatrix metalloproteinase 10,Interleukin1-alpha, andCyclo-oxygenase 2 (COX2) genes.[7]
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 theWellcome 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 promotingenzyme,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.[8][9]
TheCUX1 geneAlternativelySplicedProduct was first reported in 1997.[11][a] The CUX1 gene has up to 33exons. CASPmRNA includes exons 1 through 14 and 25 through 33.[13] The human CASP protein is predicted to contain 678amino acids, of which 400 are shared with CUTL1.[11] CASP protein is approximately 80kD.[11] It lacks the DNA binding region of CUTL1,[11][14] but instead contains a trans-membrane domain that allows it to insert into lipid bilayers.[14] It has been localized to theGolgi apparatus.[14]
CASP has been reported to be part of a complex withGolgin 84 that tethersCOPIvesicles and is important for retrograde transport in the Golgi and between the Golgi andendoplasmic reticulum.[15] The targeting of vesicles involves tethers andSNAREs.[15]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.PMID8468066.
^abcdLievens 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.PMID9332351.
^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.PMID12891711.S2CID2287673.
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.PMID2481658.
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.PMID11403998.
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.PMID1301999.S2CID37107643.
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.PMID8125298.
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.PMID9332351.
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.PMID9373149.
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.PMID10607901.
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.PMID10803519.S2CID19998783.
