View source for CUTL1

{{cs1 config|name-list-style=vanc}}
{{short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Cux1 (CUTL1, CDP, CDP/Cux)''' is a homeodomain [[protein]] that in humans is encoded by the ''CUX1'' [[gene]].<ref name="pmid8468066">{{cite journal | vauthors = Scherer SW, Neufeld EJ, Lievens PM, Orkin SH, Kim J, Tsui LC | title = Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids | journal = Genomics | volume = 15 | issue = 3 | pages = 695–6 | date = May 1993 | pmid = 8468066 | doi = 10.1006/geno.1993.1130 }}</ref><ref name="pmid9799793">{{cite journal | vauthors = Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A | title = 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 | journal = Genome Res. | volume = 8 | issue = 10 | pages = 1060–73 | date = December 1998 | pmid = 9799793 | pmc = 310788 | doi = 10.1101/gr.8.10.1060 }}</ref><ref name="pmid15004235">{{cite journal | vauthors = Oka T, Ungar D, Hughson FM, Krieger M | title = The COG and COPI Complexes Interact to Control the Abundance of GEARs, a Subset of Golgi Integral Membrane Proteins | journal = Mol. Biol. Cell | volume = 15 | issue = 5 | pages = 2423–35 | date = April 2004 | pmid = 15004235 | pmc = 404034 | doi = 10.1091/mbc.E03-09-0699 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CUTL1 cut-like 1, CCAAT displacement protein (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1523}}</ref>

== 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.<ref name="entrez" /> Cux1 DNA binding is stimulated by activation of the [[F2RL1|PAR2/F2RL1]] cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulate [[MMP10|Matrix metalloproteinase 10]], [[IL1A|Interleukin1-alpha]], and [[PTGS2|Cyclo-oxygenase 2 (COX2)]] genes.<ref name="pmid18952606">{{cite journal | vauthors = Wilson BJ, Harada R, LeDuy L, Hollenberg MD, Nepveu A | title = CUX1 transcription factor is a downstream effector of the proteinase-activated receptor 2 (PAR2) | journal = J. Biol. Chem. | volume = 284 | issue = 1 | pages = 36–45 | date = January 2009 | pmid = 18952606 | doi = 10.1074/jbc.M803808200 | doi-access = free }}</ref>

== 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.<ref>{{cite web|url= http://www.sanger.ac.uk/about/press/2013/131208.html|title=Gene promotes one in a hundred of tumours|author=Press Release|publisher=Wellcome Trust Sanger Institute|date=8 December 2013|access-date=17 December 2013}}</ref><ref>{{cite journal | vauthors = Wong CC, Martincorena I, Rust AG, Rashid M, Alifrangis C, Alexandrov LB, Tiffen JC, Kober C, Green AR, Massie CE, Nangalia J, Lempidaki S, Döhner H, Döhner K, Bray SJ, McDermott U, Papaemmanuil E, Campbell PJ, Adams DJ | title = Inactivating CUX1 mutations promote tumorigenesis | journal = Nature Genetics | volume = 46 | issue = 1 | pages = 33–8 | year = 2013 | pmid = 24316979 | doi = 10.1038/ng.2846 | display-authors = 3 | pmc=3874239}}</ref>

== CASP ==
[[File:ExternalImageImagec.jpg|thumb|[http://onlinelibrary.wiley.com/enhanced/figures/doi/10.1111/j.1600-0854.2010.01123.x#figure-viewer-f10 Model of tethering involving CASP.]<ref name="pmid20874812">{{cite journal | vauthors = Sohda M, Misumi Y, Yamamoto A, Nakamura N, Ogata S, Sakisaka S, Hirose S, Ikehara Y, Oda K | title = Interaction of Golgin-84 with the COG complex mediates the intra-Golgi retrograde transport | journal = Traffic | volume = 11 | issue = 12 | pages = 1552–66 | year = 2010 | pmid = 20874812 | doi = 10.1111/j.1600-0854.2010.01123.x | s2cid = 20424336 | doi-access = free }}</ref>]]
The '''C'''UX1 gene '''A'''lternatively '''S'''pliced '''P'''roduct was first reported in 1997.<ref name="pmid9332351">{{cite journal | vauthors = Lievens PM, Tufarelli C, Donady JJ, Stagg A, Neufeld EJ | title = 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 | journal = Gene | volume = 197 | issue = 1–2 | pages = 73–81 | year = 1997 | pmid = 9332351 | doi = 10.1016/s0378-1119(97)00243-6}}</ref>{{efn|This CASP is not the same as the scaffolding protein called CASP<ref name="pmid12052827">{{cite journal | vauthors = Mansour M, Lee SY, Pohajdak B | title = The N-terminal coiled coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with the scaffolding protein CASP | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 32302–9 | year = 2002 | pmid = 12052827 | doi = 10.1074/jbc.M202898200 | doi-access =free  }}</ref> for '''C'''ytohesin/'''A'''RNO ... '''S'''caffolding '''P'''rotein}} The CUX1 gene has up to 33 [[exon]]s. CASP [[mRNA]] includes exons 1 through 14 and 25 through 33.<ref name="pmid25190083">{{cite journal | vauthors = Ramdzan ZM, Nepveu A | title = CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers | journal = Nature Reviews Cancer | volume = 14 | issue = 10 | pages = 673–82 | year = 2014 | pmid = 25190083 | doi = 10.1038/nrc3805 | s2cid = 20468440 | url = http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=145247}}</ref> The human CASP protein is predicted to contain 678 [[amino acids]], of which 400 are shared with CUTL1.<ref name="pmid9332351"/> CASP protein is approximately 80 [[Kilo-|k]][[Dalton (unit)|D]].<ref name="pmid9332351"/> It lacks the DNA binding region of CUTL1,<ref name="pmid9332351"/><ref name="pmid12429822">{{cite journal | vauthors = Gillingham AK, Pfeifer AC, Munro S | title = CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin | journal = Molecular Biology of the Cell | volume = 13 | issue = 11 | pages = 3761–74 | year = 2002 | pmid = 12429822 | pmc = 133590 | doi = 10.1091/mbc.E02-06-0349 }}</ref> but instead contains a trans-membrane domain that allows it to insert into lipid bilayers.<ref name="pmid12429822"/> It has been localized to the [[Golgi apparatus]].<ref name="pmid12429822"/>

CASP has been reported to be part of a complex with [[GOLGA5|Golgin 84]] that tethers [[COPI]] [[Vesicle (biology and chemistry)|vesicles]] and is important for retrograde transport in the Golgi and between the Golgi and [[endoplasmic reticulum]].<ref name="pmid15718469">{{cite journal | vauthors = Malsam J, Satoh A, Pelletier L, Warren G | title = Golgin tethers define subpopulations of COPI vesicles | journal = Science | volume = 307 | issue = 5712 | pages = 1095–8 | year = 2005 | pmid = 15718469 | doi = 10.1126/science.1108061 | bibcode = 2005Sci...307.1095M | s2cid = 12601850 }}</ref> The targeting of vesicles involves tethers and [[SNARE]]s.<ref name="pmid15718469"/>

== Interactions ==
[[File:BioPlexCUX1c.jpg|thumb|The CUX1 network identified in the [http://bioplex.hms.harvard.edu/bioplexDisplay/index.php BioPlex searchable website.] ]]
Cux1 (CUTL1, CDP, CDP/Cux) has been shown to [[Protein-protein interaction|interact]] with:
* [[CREB binding protein]],<ref name = pmid10852958>{{cite journal | vauthors = Li S, Aufiero B, Schiltz RL, Walsh MJ | title = Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 13 | pages = 7166–71 | date = June 2000 | pmid = 10852958 | pmc = 16517 | doi = 10.1073/pnas.130028697 | bibcode = 2000PNAS...97.7166L | doi-access = free }}</ref> 
* [[Retinoblastoma protein]],<ref name = pmid12891711>{{cite journal | vauthors = Gupta S, Luong MX, Bleuming SA, Miele A, Luong M, Young D, Knudsen ES, Van Wijnen AJ, Stein JL, Stein GS | title = Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription | journal = J. Cell. Physiol. | volume = 196 | issue = 3 | pages = 541–56 | date = September 2003 | pmid = 12891711 | doi = 10.1002/jcp.10335 | s2cid = 2287673 }}</ref> and
* [[SATB1]]<ref name = pmid10373541>{{cite journal | vauthors = Liu J, Barnett A, Neufeld EJ, Dudley JP | title = Homeoproteins CDP and SATB1 interact: potential for tissue-specific regulation | journal = Mol. Cell. Biol. | volume = 19 | issue = 7 | pages = 4918–26 | date = July 1999 | pmid = 10373541 | pmc = 84297 | doi =  10.1128/mcb.19.7.4918}}</ref>

These physical interactions are reported in [[BioPlex]] 2.0
{{div col|colwidth=30em}}
*[[MAGEA10]]
*[[EXT2 (gene)|EXT2]]
*[[RAB30]]
*[[HLA-DQA1]]
*[[STX6]]
*[[WDR83]]
*[[SLC39A4]]
*[[LAMP1]]
*[[POTEB]]
*[[SLC39A12]]
{{div col end}}

== Notes==
{{notelist}}

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin|35em}}
* {{cite journal | vauthors = Ottolenghi S, Mantovani R, Nicolis S, Ronchi A, Giglioni B | title = DNA sequences regulating human globin gene transcription in nondeletional hereditary persistence of fetal hemoglobin | journal = Hemoglobin | volume = 13 | issue = 6 | pages = 523–41 | year = 1990 | pmid = 2481658 | doi = 10.3109/03630268908993104 }}
* {{cite journal | vauthors = Nepveu A | title = Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development | journal = Gene | volume = 270 | issue = 1–2 | pages = 1–15 | year = 2001 | pmid = 11403998 | doi = 10.1016/S0378-1119(01)00485-1 }}
* {{cite journal | vauthors = Neufeld EJ, Skalnik DG, Lievens PM, Orkin SH | title = Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut | journal = Nat. Genet. | volume = 1 | issue = 1 | pages = 50–5 | year = 1993 | pmid = 1301999 | doi = 10.1038/ng0492-50 | s2cid = 37107643 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Chernousov MA, Stahl RC, Carey DJ | title = Schwann cells secrete a novel collagen-like adhesive protein that binds N-syndecan | journal = J. Biol. Chem. | volume = 271 | issue = 23 | pages = 13844–53 | year = 1996 | pmid = 8662884 | doi = 10.1074/jbc.271.23.13844 | doi-access = free }}
* {{cite journal | vauthors = Lievens PM, Tufarelli C, Donady JJ, Stagg A, Neufeld EJ | title = 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 | journal = Gene | volume = 197 | issue = 1–2 | pages = 73–81 | year = 1997 | pmid = 9332351 | doi = 10.1016/S0378-1119(97)00243-6 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Chattopadhyay S, Whitehurst CE, Chen J | title = 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 | journal = J. Biol. Chem. | volume = 273 | issue = 45 | pages = 29838–46 | year = 1998 | pmid = 9792700 | doi = 10.1074/jbc.273.45.29838 | doi-access = free }}
* {{cite journal | vauthors = Liu J, Barnett A, Neufeld EJ, Dudley JP | title = Homeoproteins CDP and SATB1 Interact: Potential for Tissue-Specific Regulation | journal = Mol. Cell. Biol. | volume = 19 | issue = 7 | pages = 4918–26 | year = 1999 | pmid = 10373541 | pmc = 84297 | doi =  10.1128/mcb.19.7.4918}}
* {{cite journal | vauthors = Rong Zeng W, Soucie E, Sung Moon N, Martin-Soudant N, Bérubé G, Leduy L, Nepveu A | title = Exon/intron structure and alternative transcripts of the CUTL1 gene | journal = Gene | volume = 241 | issue = 1 | pages = 75–85 | year = 2000 | pmid = 10607901 | doi = 10.1016/S0378-1119(99)00465-5 }}
* {{cite journal | vauthors = Martin-Soudant N, Drachman JG, Kaushansky K, Nepveu A | title = CDP/Cut DNA binding activity is down-modulated in granulocytes, macrophages and erythrocytes but remains elevated in differentiating megakaryocytes | journal = Leukemia | volume = 14 | issue = 5 | pages = 863–73 | year = 2000 | pmid = 10803519 | doi = 10.1038/sj.leu.2401764 | s2cid = 19998783 | doi-access =  }}
* {{cite journal | vauthors = Li S, Aufiero B, Schiltz RL, Walsh MJ | title = Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 13 | pages = 7166–71 | year = 2000 | pmid = 10852958 | pmc = 16517 | doi = 10.1073/pnas.130028697 | bibcode = 2000PNAS...97.7166L | doi-access = free }}
* {{cite journal | vauthors = Nirodi C, Hart J, Dhawan P, Moon NS, Nepveu A, Richmond A | title = The Role of CDP in the Negative Regulation of CXCL1 Gene Expression | journal = J. Biol. Chem. | volume = 276 | issue = 28 | pages = 26122–31 | year = 2001 | pmid = 11371564 | pmc = 2665279 | doi = 10.1074/jbc.M102872200 | doi-access = free }}
* {{cite journal | vauthors = Moon NS, Premdas P, Truscott M, Leduy L, Bérubé G, Nepveu A | title = S Phase-Specific Proteolytic Cleavage Is Required To Activate Stable DNA Binding by the CDP/Cut Homeodomain Protein | journal = Mol. Cell. Biol. | volume = 21 | issue = 18 | pages = 6332–45 | year = 2001 | pmid = 11509674 | pmc = 87367 | doi = 10.1128/MCB.21.18.6332-6345.2001 }}
* {{cite journal | vauthors = Santaguida M, Ding Q, Bérubé G, Truscott M, Whyte P, Nepveu A | title = Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2) | journal = J. Biol. Chem. | volume = 276 | issue = 49 | pages = 45780–90 | year = 2002 | pmid = 11584018 | doi = 10.1074/jbc.M107978200  |doi-access=free }}
* {{cite journal | vauthors = Dintilhac A, Bernués J | title = HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences | journal = J. Biol. Chem. | volume = 277 | issue = 9 | pages = 7021–8 | year = 2002 | pmid = 11748221 | doi = 10.1074/jbc.M108417200 | s2cid = 39560486 | url = https://digital.csic.es/bitstream/10261/112516/4/jbc.M108417200.full.pdf | doi-access = free }}
{{refend}}

== External links ==
* {{MeshName|CUTL1+protein,+human}}
* {{UCSC gene info|CUX1}}

{{NLM content}}
{{Transcription factors|g3}}

[[Category:Transcription factors]]