CUTL1

CUX1
Identifiers
Aliases CUX1, CASP, CDP, CDP/Cut, CDP1, COY1, CUTL1, CUX, Clox, Cux/CDP, GOLIM6, Nbla10317, p100, p110, p200, p75, cut like homeobox 1
External IDs HomoloGene: 22551 GeneCards: CUX1
Orthologs
Species Human Mouse
Entrez

1523

n/a

Ensembl

ENSG00000257923

n/a

UniProt

P39880
Q13948

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC) Chr 7: 101.82 – 102.28 Mb n/a
PubMed search [1] n/a
Wikidata
View/Edit Human

Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.[2][3][4][5]

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.[5] 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.[6]

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.[7][8]

Interactions

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

References

  1. "Human PubMed Reference:".
  2. 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.
  3. 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 310788Freely accessible. PMID 9799793.
  4. 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 404034Freely accessible. PMID 15004235.
  5. 1 2 "Entrez Gene: CUTL1 cut-like 1, CCAAT displacement protein (Drosophila)".
  6. 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.
  7. Press Release (8 December 2013). "Gene promotes one in a hundred of tumours". Wellcome Trust Sanger Institute. Retrieved 17 December 2013.
  8. 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.
  9. 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 16517Freely accessible. PMID 10852958.
  10. 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.
  11. 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 84297Freely accessible. PMID 10373541.

Further reading

External links

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

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