CUTL1
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| Location (UCSC) | Chr 7: 101.82 – 102.28 Mb | n/a | |||||||
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Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.[3][4][5][6]
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.Cyclo-oxygenase 2 (COX2) genes.[7]
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.[8][9]
CASP
The CUX1 gene Alternatively Spliced Product was first reported in 1997.
CASP has been reported to be part of a complex with
SNAREs.[15]
Interactions
Cux1 (CUTL1, CDP, CDP/Cux) has been shown to
interact
with:
- CREB binding protein,[16]
- Retinoblastoma protein,[17] and
- SATB1[18]
These physical interactions are reported in BioPlex 2.0
Notes
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000257923 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8468066.
- PMID 9799793.
- PMID 15004235.
- ^ a b "Entrez Gene: CUTL1 cut-like 1, CCAAT displacement protein (Drosophila)".
- PMID 18952606.
- ^ Press Release (8 December 2013). "Gene promotes one in a hundred of tumours". Wellcome Trust Sanger Institute. Retrieved 17 December 2013.
- PMID 24316979.
- S2CID 20424336.
- ^ PMID 9332351.
- PMID 12052827.
- S2CID 20468440.
- ^ PMID 12429822.
- ^ S2CID 12601850.
- PMID 10852958.
- S2CID 2287673.
- 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. 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. 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. S2CID 37107643.
- 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. 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. 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. 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. 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. 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. 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. 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. S2CID 19998783.
- 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. 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. 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. 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. PMID 11584018.
- Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences" (PDF). J. Biol. Chem. 277 (9): 7021–8. S2CID 39560486.
External links
- CUTL1+protein,+human at the U.S. 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.