CUTL1

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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 OMIM116896 MGI88568 HomoloGene22551 GeneCards: CUX1 Gene
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:
101.46 – 101.93 Mb
Chr 5:
136.25 – 136.57 Mb
PubMed search [1] [2]

Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.1234

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

Interactions

Cux1 (CUTL1, CDP, CDP/Cux) has been shown to interact with CREB binding protein,6 SATB17 and Retinoblastoma protein.8

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. 9 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. ^ Glockner 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. ^ a b "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. ^ Li, S; Aufiero B; Schiltz R L; Walsh M J (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. (UNITED STATES) 97 (13): 7166–71. doi:10.1073/pnas.130028697. ISSN 0027-8424. PMC 16517. PMID 10852958. 
  7. ^ Liu, J; Barnett A; Neufeld E J; Dudley J P (July 1999). "Homeoproteins CDP and SATB1 Interact: Potential for Tissue-Specific Regulation". Mol. Cell. Biol. (UNITED STATES) 19 (7): 4918–26. ISSN 0270-7306. PMC 84297. PMID 10373541. 
  8. ^ Gupta, Sunita; Luong Mai X; Bleuming Sylvia A; Miele Angela; Luong Michael; Young Daniel; Knudsen Erik S; Van Wijnen Andre J; Stein Janet L; Stein Gary S (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. (United States) 196 (3): 541–56. doi:10.1002/jcp.10335. ISSN 0021-9541. PMID 12891711. 
  9. ^ Press Release (8 December 2013). "Gene promotes one in a hundred of tumours". Wellcome Trust Sanger Institute. Retrieved 17 December 2013. 
  10. ^ Wong, Chi; Adams, David; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium et al. (2013). "Inactivating CUX1 mutations promote tumorigenesis". Nature Genetics. doi:10.1038/ng.2846. PMID 24316979. 

Further reading

External links

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