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CUX1 (cut-like homeobox 1)

Written2011-10Benjamin Kühnemuth, Patrick Michl
Department of Gastroenterology, Endocrinology, University of Marburg, Marburg, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCUTL1
cut (Drosophila)-like 1 (CCAAT displacement protein)
cut-like 1, CCAAT displacement protein (Drosophila)
cut-like homeobox 1
Alias_symbol (synonym)CDP
CDP1
CUX
CUT
Clox
CDP/Cut
CDP/Cux
Cux/CDP
CASP
GOLIM6
Other aliasCOY1
FLJ31745
Nbla10317
p100
p110
p200
p75
HGNC (Hugo) CUX1
LocusID (NCBI) 1523
Atlas_Id 403
Location 7q22.1  [Link to chromosome band 7q22]
Location_base_pair Starts at 101815904 and ends at 102258233 bp from pter ( according to hg19-Feb_2009)  [Mapping CUX1.png]
Fusion genes
(updated 2016)
CUX1 (7q22.1) / ACAP2 (3q29)CUX1 (7q22.1) / ACHE (7q22.1)CUX1 (7q22.1) / AGR3 (7p21.1)
CUX1 (7q22.1) / AHCYL2 (7q32.1)CUX1 (7q22.1) / ANPEP (15q26.1)CUX1 (7q22.1) / ATM (11q22.3)
CUX1 (7q22.1) / CDC42 (1p36.12)CUX1 (7q22.1) / CUX1 (7q22.1)CUX1 (7q22.1) / EHBP1L1 (11q13.1)
CUX1 (7q22.1) / FGFR1 (8p11.23)CUX1 (7q22.1) / GINS3 (16q21)CUX1 (7q22.1) / GNAS (20q13.32)
CUX1 (7q22.1) / MARCH10 (17q23.2)CUX1 (7q22.1) / MSI2 (17q22)CUX1 (7q22.1) / MTMR7 (8p22)
CUX1 (7q22.1) / NUP98 (11p15.4)CUX1 (7q22.1) / NUTM1 (15q14)CUX1 (7q22.1) / RET (10q11.21)
CUX1 (7q22.1) / THSD7A (7p21.3)CUX1 (7q22.1) / WNT7A (3p25.1)CWC22 (2q31.3) / CUX1 (7q22.1)
DDX54 (12q24.13) / CUX1 (7q22.1)GSK3B (3q13.33) / CUX1 (7q22.1)MAP2K1 (15q22.31) / CUX1 (7q22.1)
NUP98 (11p15.4) / CUX1 (7q22.1)ORAI2 (7q22.1) / CUX1 (7q22.1)RAB37 (17q25.1) / CUX1 (7q22.1)
RPL41 (12q13.2) / CUX1 (7q22.1)STK17B (2q32.3) / CUX1 (7q22.1)SURF4 (9q34.2) / CUX1 (7q22.1)
TMEM14B (6p24.2) / CUX1 (7q22.1)ZSCAN25 (7q22.1) / CUX1 (7q22.1)

DNA/RNA

Description The human CUX1 gene is located on chromosome 7q22 (Scherer et al., 1993). It comprises 33 exons and spans 468 kb.
Five alternative splice variants have been identified. Most of the splicing sites are located in the regions downstream of exon 14 and 15 (Rong Zeng et al., 2000). Two alternative sites for transcript termination have been identified. Termination at UGA in exon 24 leads to production of CUX1 mRNA comprising exon 1-24. Elongation up to exon 33 results in alternative splicing and the production of CASP mRNA comprising exon 1-15 and 25-33 (Lievens et al., 1997; Rong Zeng et al., 2000).
The first transcriptional start site is located in exon 1 but transcription can be initiated at several sites in a 200 bp region upstream of exon 1 (Rong Zeng et al., 2000). Initiation within intron 20 leads to production of an mRNA coding for the shortened p75 isoform (Goulet et al., 2002).
Several putative translation initiation codons can be found in exon 1 but ATG at position 550 has been described as the predominant initiation site (Rong Zeng et al., 2000).

Protein

 
  Cux1 isoforms. The p75 isoform is the product of a shortened mRNA that is generated by the use of an alternative transcriptional start site. In contrast, the p150, p110, p90 and p80 isoforms are produced by proteolytic processing of the full length protein (p200). CR = cut repeat; HD = homeodomain.
Description The human full length CUX1 protein (p200) consists of 1505 amino acids and contains four DNA binding domains: three CUT-repeats and one CUT-homeodomain (Harada et al., 1994).
Several shortened CUX1 isoforms have been described that are named according to their molecular weight. CUX1 p75 is the product of a shortened mRNA that is generated by the use of an alternative transcription start site in exon 20 (Rong Zeng et al., 2000; Goulet et al., 2002). CUX1 p150, p110, p90 and p80 are generated by proteolytic processing of the full length protein by a nuclear isoform of Cathepsin L and other not yet identified proteases such as caspases (Goulet et al., 2004; Goulet et al., 2006; Maitra et al., 2006; Truscott et al., 2007).
The presence of DNA binding domains in the CUX1 isoforms determines their interaction with DNA and their transcriptional activity. The full length protein p200 shows unstable DNA binding, carries the CCAAT-displacement activity and functions predominantly as a transcriptional repressor. In contrast, the p110, p90, p80 and p75 isoforms show stable DNA binding and function both as transcriptional repressors or activators (Truscott et al., 2004; Goulet et al., 2002; Goulet et al., 2006; Moon et al., 2001). According to Maitra et al., the p150 isoform is incapable of DNA binding (Maitra et al., 2006).
Several posttranslational modifications are known to modulate the DNA binding activities of the CUX1 proteins. Protein kinase C and Casein kinase II are able to phosphorylate serine or threonine residues within the cut repeats (Coqueret et al., 1998b; Li et al., 2007). Protein kinase A and cyclin A/Cdk1 phosphorylate specific serine residues in a region between the Cut repeat 3 and the homeodomain (Michl et al., 2006; Santaguida et al., 2001). PCAF acetyl-transferase is able to acetylate CUX1 on a lysine residue in the homeodomain (Li et al., 2000). Both, phosphorylation and acetylation have been shown to inhibit CUX1 DNA binding (Sansregret et al., 2010; Li et al., 2000). Consistent with this, dephosphorylation by Cdc 25A phosphatase is able to increase DNA binding of CUX1 (Coqueret et al, 1998a).
Expression Early studies suggested that in mammalian cells, CUX1 represses genes that are upregulated in differentiated tissues. Furthermore, the expression of CUX1 might be restricted to proliferating and undifferentiated cells and is inversely related to the degree of differentiation (vanden Heuvel et al., 1996; Pattison et al., 1997; van Gurp et al., 1999). More recently however, studies in mice revealed that CUX1 is also expressed in terminally differentiated cells of many tissues (Khanna-Gupta et al., 2001; Ellis et al., 2001).
Increased CUX1 expression was found in various tumour types including multiple myelomas, acute lymphoblastic leukaemia, breast carcinoma and pancreatic cancer (De Vos et al., 2002; Tsutsumi et al., 2003; Michl et al., 2005; Ripka et al., 2007).
It has been shown that the cellular expression of CUX1 mRNA and protein is elevated following TGF-beta stimulation in many cell types including fibroblasts, pancreatic cancer cells, breast cancer cells and malignant plasma cells (Fragiadaki et al., 2011; Michl et al., 2005; De Vos et al., 2002). This regulation of CUX1 expression by TGF-beta is probably mediated by p38MAPK and Smad4 signalling (Michl et al., 2005).
Localisation Studies indicate that phosphorylated CUX1 is preferentially localized in the cytoplasm whereas dephosphorylation leads to translocation into the nucleus (Sansregret et al., 2010).
Function The vast majority of studies describes CUX1 as a transcriptional repressor (Lievens et al., 1995; Ai et al., 1999; Catt et al., 1999a; Catt et al., 1999b; Ueda et al., 2007). The repressor activity can be mediated by competition for DNA binding sites with transcriptional activators (Kim et al., 1997; Stünkel et al., 2000), by recruitment of histone deacetylases (Li et al., 1999) or by recruitment of histone lysine methyltransferases (Nishio and Walsh, 2004). CUX1 may also negatively regulate gene expression by binding to matrix attachment regions and by modulating their association with the nuclear scaffold (Banan et al., 1997; Stünkel et al., 2000; Goebel et al., 2002; Kaul-Ghanekar et al., 2004). In contrast, the mechanisms underlying its effects on transcriptional activation are less well understood.
CUX1 is involved in at least three cellular processes important for cancer progression: cell proliferation, cell motility/invasiveness and apoptosis.

Proliferation
Studies indicate that the pro-proliferative effects of CUX1 are mainly mediated by the p110 isoform. This isoform is produced by proteolytic cleavage of the full length protein occuring during G1/S-transition in the cell cycle (Goulet et al., 2004; Moon et al., 2001). Cells stably transfected with p110 CUX1 showed increased proliferation due to a shortened G1-phase whereas embryonic fibroblasts obtained from CUX1 knockout mice showed elongated G1-phase and less proliferation compared to cells isolated from wild-type mice (Sansregret et al., 2006).
A genome-wide location array for p110 CUX1 binding sites in transformed and non-transformed cell lines identified numerous CUX1 target genes that are related to proliferation and cell cycle progression (Harada et al., 2008). Most of these genes are activated by p110 CUX1 including DNA polymerase-alpha, cyclin A2 and cyclin E2. In contrast, other genes are repressed such as the CDK-inhibitor p21 (Truscott et al., 2003; Nishio and Walsh, 2004; Harada et al., 2008).

Cell motility
First evidence that CUX1 plays a role in cell motility originates from knockdown studies in fibroblasts and a panel of human cancer cell lines that revealed that depletion of CUX1 leads to decreased cell migration and invasion (Michl et al., 2005). In agreement with this, cells stably expressing p110 and p75 CUX1 show increased cell migration and invasion (Kedinger et al., 2009; Cadieux et al., 2009). Additionally, tail vein injection of cells stably expressing shRNA against CUX1 resulted in reduced formation of lung metastases, whereas injection of cells stably overexpressing CUX1 led to increased lung metastases (Michl et al., 2005; Cadieux et al., 2009).
The molecular basis for these effects on cell motility was in part elucidated in a genome-wide location analysis in several cell lines (Kedinger et al., 2009). In this study, CUX1 was found to inhibit the expression of genes that repress cell migration (e.g. E-cadherin, occludin) and to turn on the expression of genes that promote cell migration (e.g. FAK, N-cadherin, vimentin) (Kedinger et al., 2009). The regulation of these genes seems to be mediated both directly by binding of CUX1 to the gene promoters but also indirectly by modulation of transcription factors and signaling proteins involved in EMT (e.g. SNAI1, SNAI2, Src, Wnt5a) (Kedinger et al., 2009; Aleksic et al., 2007; Ripka et al., 2007). Additionally, several of the CUX1 target genes are known GTPases important for actin-cytoskeleton polymerization (Kedinger et al., 2009).

Apoptosis
Studies in pancreatic cancer cell lines showed that depletion of CUX1 by siRNA increases TNFalpha- and TRAIL-induced apoptosis whereas overexpression of CUX1 rescues from apoptosis. Additionally, treatment of xenograft tumours with siRNA for CUX1 lead to retarded tumour growth and increased apoptosis. These effects are at least in part explained by a positive regulation of the antiapoptotic protein BCL2 by CUX1 (Ripka et al., 2010a). Subsequently, the glutamate receptor GRIA3 was identified as another downstream target of CUX1 able to mediate its antiapoptotic effects (Ripka et al., 2010b).

Homology Cut homeodomain proteins are highly conserved in evolution of metazoans. Homologues of the Drosophila melanogaster Cut protein have been described at least in human, dog and mouse (Neufeld et al., 1992; Andres et al., 1992; Valarché et al., 1993). In humans, a homologue gene, called CUX2, was described (Jacobsen et al., 2001).

Mutations

Note A missense mutation affecting the homeodomain has been described in one patient suffering from acute myeloid leukaemia, the significance of which remains to be elucidated (Thoennissen et al., 2011).

Implicated in

Note
  
Entity Pancreatic cancer
Note In pancreatic cancer CUX1 expression is elevated compared to normal pancreas tissue (Ripka et al., 2010a). Furthermore, an increased expression in high-grade tumours compared to low grade tumours was described (Michl et al., 2005).
The expression of CUX1 is accompanied by the overexpression of its downstream targets WNT5a and GRIA3 that, at least in part, mediate the proinvasive and proproliferative effects of CUX1 (Ripka et al., 2006; Ripka et al., 2010b).
Antiapoptotic effects of CUX1 in pancreatic cancer, that have been shown in in vitro studies and in xenograft models, are associated with a positive regulation of BCL2 and downregulation of tumour necrosis factor alpha and are, at least in part, mediated by the glutamate receptor GRIA3 (Ripka et al., 2010a; Ripka et al., 2010b).
  
  
Entity Breast cancer
Note In mammary carcinoma the CUX1 expression is increased in high-grade tumours compared to low grade tumours and a reverse correlation between CUX1 mRNA levels and the relapse free- and overall-survival was shown (Michl et al., 2005). Furthermore, is has been shown that the expression levels of the intron 20-initiated mRNA, that leads to the synthesis of the p75 CUX1 isoform, is specifically expressed in breast cancer and positively correlated with a diffuse infiltrative growth pattern (Goulet et al., 2002). Transgenic mice expressing p75 and p110 CUX1 under the control of the mouse mammary tumour virus-long terminal repeat developed breast cancer after a long latency period. This tumour development was accompanied by an increased activity of WNT-β-catenin signalling (Cadieux et al., 2009).
Oncogenesis .
  

Bibliography

CCAAT displacement protein binds to and negatively regulates human papillomavirus type 6 E6, E7, and E1 promoters.
Ai W, Toussaint E, Roman A.
J Virol. 1999 May;73(5):4220-9.
PMID 10196318
 
CUTL1 promotes tumor cell migration by decreasing proteasome-mediated Src degradation.
Aleksic T, Bechtel M, Krndija D, von Wichert G, Knobel B, Giehl K, Gress TM, Michl P.
Oncogene. 2007 Aug 30;26(40):5939-49. Epub 2007 Mar 19.
PMID 17369846
 
Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding regulatory proteins differentially expressed during development.
Andres V, Nadal-Ginard B, Mahdavi V.
Development. 1992 Oct;116(2):321-34.
PMID 1363085
 
Interaction of the nuclear matrix-associated region (MAR)-binding proteins, SATB1 and CDP/Cux, with a MAR element (L2a) in an upstream regulatory region of the mouse CD8a gene.
Banan M, Rojas IC, Lee WH, King HL, Harriss JV, Kobayashi R, Webb CF, Gottlieb PD.
J Biol Chem. 1997 Jul 18;272(29):18440-52.
PMID 9218488
 
Mouse mammary tumor virus p75 and p110 CUX1 transgenic mice develop mammary tumors of various histologic types.
Cadieux C, Kedinger V, Yao L, Vadnais C, Drossos M, Paquet M, Nepveu A.
Cancer Res. 2009 Sep 15;69(18):7188-97. Epub 2009 Sep 8.
PMID 19738070
 
Overexpression of CCAAT displacement protein represses the promiscuously active proximal gp91(phox) promoter.
Catt D, Hawkins S, Roman A, Luo W, Skalnik DG.
Blood. 1999a Nov 1;94(9):3151-60.
PMID 10556202
 
DNA-binding properties of CCAAT displacement protein cut repeats.
Catt D, Luo W, Skalnik DG.
Cell Mol Biol (Noisy-le-grand). 1999b Dec;45(8):1149-60.
PMID 10643964
 
DNA binding by cut homeodomain proteins is down-modulated by casein kinase II.
Coqueret O, Martin N, Berube G, Rabbat M, Litchfield DW, Nepveu A.
J Biol Chem. 1998b Jan 30;273(5):2561-6.
PMID 9446557
 
Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays.
De Vos J, Thykjaer T, Tarte K, Ensslen M, Raynaud P, Requirand G, Pellet F, Pantesco V, Reme T, Jourdan M, Rossi JF, Orntoft T, Klein B.
Oncogene. 2002 Oct 3;21(44):6848-57.
PMID 12360412
 
The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle.
Ellis T, Gambardella L, Horcher M, Tschanz S, Capol J, Bertram P, Jochum W, Barrandon Y, Busslinger M.
Genes Dev. 2001 Sep 1;15(17):2307-19.
PMID 11544187
 
High doses of TGF-beta potently suppress type I collagen via the transcription factor CUX1.
Fragiadaki M, Ikeda T, Witherden A, Mason RM, Abraham D, Bou-Gharios G.
Mol Biol Cell. 2011 Jun 1;22(11):1836-44. Epub 2011 Apr 6.
PMID 21471005
 
High frequency of matrix attachment regions and cut-like protein x/CCAAT-displacement protein and B cell regulator of IgH transcription binding sites flanking Ig V region genes.
Goebel P, Montalbano A, Ayers N, Kompfner E, Dickinson L, Webb CF, Feeney AJ.
J Immunol. 2002 Sep 1;169(5):2477-87.
PMID 12193717
 
A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor.
Goulet B, Baruch A, Moon NS, Poirier M, Sansregret LL, Erickson A, Bogyo M, Nepveu A.
Mol Cell. 2004 Apr 23;14(2):207-19.
PMID 15099520
 
A novel proteolytically processed CDP/Cux isoform of 90 kDa is generated by cathepsin L.
Goulet B, Truscott M, Nepveu A.
Biol Chem. 2006 Sep;387(9):1285-93.
PMID 16972798
 
Characterization of a tissue-specific CDP/Cux isoform, p75, activated in breast tumor cells.
Goulet B, Watson P, Poirier M, Leduy L, Berube G, Meterissian S, Jolicoeur P, Nepveu A.
Cancer Res. 2002 Nov 15;62(22):6625-33.
PMID 12438259
 
Conserved cut repeats in the human cut homeodomain protein function as DNA binding domains.
Harada R, Dufort D, Denis-Larose C, Nepveu A.
J Biol Chem. 1994 Jan 21;269(3):2062-7.
PMID 7904999
 
Genome-wide location analysis and expression studies reveal a role for p110 CUX1 in the activation of DNA replication genes.
Harada R, Vadnais C, Sansregret L, Leduy L, Berube G, Robert F, Nepveu A.
Nucleic Acids Res. 2008 Jan;36(1):189-202. Epub 2007 Nov 14.
PMID 18003658
 
CUX2, a potential regulator of NCAM expression: genomic characterization and analysis as a positional candidate susceptibility gene for bipolar disorder.
Jacobsen NJ, Elvidge G, Franks EK, O'Donovan MC, Craddock N, Owen MJ.
Am J Med Genet. 2001 Apr 8;105(3):295-300.
PMID 11353453
 
SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRbeta enhancer (Ebeta).
Kaul-Ghanekar R, Jalota A, Pavithra L, Tucker P, Chattopadhyay S.
Nucleic Acids Res. 2004 Sep 15;32(16):4862-75. Print 2004.
PMID 15371550
 
p110 CUX1 homeodomain protein stimulates cell migration and invasion in part through a regulatory cascade culminating in the repression of E-cadherin and occludin.
Kedinger V, Sansregret L, Harada R, Vadnais C, Cadieux C, Fathers K, Park M, Nepveu A.
J Biol Chem. 2009 Oct 2;284(40):27701-11. Epub 2009 Jul 27.
PMID 19635798
 
C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut).
Khanna-Gupta A, Zibello T, Sun H, Lekstrom-Himes J, Berliner N.
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8000-5.
PMID 11438745
 
Positive and negative regulation of the human thymidine kinase promoter mediated by CCAAT binding transcription factors NF-Y/CBF, dbpA, and CDP/cut.
Kim EC, Lau JS, Rawlings S, Lee AS.
Cell Growth Differ. 1997 Dec;8(12):1329-38.
PMID 9419421
 
Protein kinase C-mediated modulation of FIH-1 expression by the homeodomain protein CDP/Cut/Cux.
Li J, Wang E, Dutta S, Lau JS, Jiang SW, Datta K, Mukhopadhyay D.
Mol Cell Biol. 2007 Oct;27(20):7345-53. Epub 2007 Aug 6.
PMID 17682059
 
Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP.
Li S, Aufiero B, Schiltz RL, Walsh MJ.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7166-71.
PMID 10852958
 
Transcriptional repression of the cystic fibrosis transmembrane conductance regulator gene, mediated by CCAAT displacement protein/cut homolog, is associated with histone deacetylation.
Li S, Moy L, Pittman N, Shue G, Aufiero B, Neufeld EJ, LeLeiko NS, Walsh MJ.
J Biol Chem. 1999 Mar 19;274(12):7803-15.
PMID 10075672
 
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.
Lievens PM, Tufarelli C, Donady JJ, Stagg A, Neufeld EJ.
Gene. 1997 Sep 15;197(1-2):73-81.
PMID 9332351
 
Differentiation-induced cleavage of Cutl1/CDP generates a novel dominant-negative isoform that regulates mammary gene expression.
Maitra U, Seo J, Lozano MM, Dudley JP.
Mol Cell Biol. 2006 Oct;26(20):7466-78. Epub 2006 Aug 5.
PMID 17015474
 
CUTL1: a key mediator of TGFbeta-induced tumor invasion.
Michl P, Downward J.
Cell Cycle. 2006 Jan;5(2):132-4. Epub 2006 Jan 16.
PMID 16357536
 
CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness.
Michl P, Ramjaun AR, Pardo OE, Warne PH, Wagner M, Poulsom R, D'Arrigo C, Ryder K, Menke A, Gress T, Downward J.
Cancer Cell. 2005 Jun;7(6):521-32.
PMID 15950902
 
S phase-specific proteolytic cleavage is required to activate stable DNA binding by the CDP/Cut homeodomain protein.
Moon NS, Premdas P, Truscott M, Leduy L, Berube G, Nepveu A.
Mol Cell Biol. 2001 Sep;21(18):6332-45.
PMID 11509674
 
Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut.
Neufeld EJ, Skalnik DG, Lievens PM, Orkin SH.
Nat Genet. 1992 Apr;1(1):50-5.
PMID 1301999
 
CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription.
Nishio H, Walsh MJ.
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11257-62. Epub 2004 Jul 21.
PMID 15269344
 
The differentiation-specific factor CDP/Cut represses transcription and replication of human papillomaviruses through a conserved silencing element.
O'Connor MJ, Stunkel W, Koh CH, Zimmermann H, Bernard HU.
J Virol. 2000 Jan;74(1):401-10.
PMID 10590129
 
CCAAT displacement protein, a regulator of differentiation-specific gene expression, binds a negative regulatory element within the 5' end of the human papillomavirus type 6 long control region.
Pattison S, Skalnik DG, Roman A.
J Virol. 1997 Mar;71(3):2013-22.
PMID 9032333
 
WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer.
Ripka S, Konig A, Buchholz M, Wagner M, Sipos B, Kloppel G, Downward J, Gress T, Michl P.
Carcinogenesis. 2007 Jun;28(6):1178-87. Epub 2007 Jan 16.
PMID 17227781
 
CUX1: target of Akt signalling and mediator of resistance to apoptosis in pancreatic cancer.
Ripka S, Neesse A, Riedel J, Bug E, Aigner A, Poulsom R, Fulda S, Neoptolemos J, Greenhalf W, Barth P, Gress TM, Michl P.
Gut. 2010a Aug;59(8):1101-10. Epub 2010 May 4.
PMID 20442202
 
Glutamate receptor GRIA3--target of CUX1 and mediator of tumor progression in pancreatic cancer.
Ripka S, Riedel J, Neesse A, Griesmann H, Buchholz M, Ellenrieder V, Moeller F, Barth P, Gress TM, Michl P.
Neoplasia. 2010b Aug;12(8):659-67.
PMID 20689760
 
Exon/intron structure and alternative transcripts of the CUTL1 gene.
Rong Zeng W, Soucie E, Sung Moon N, Martin-Soudant N, Berube G, Leduy L, Nepveu A.
Gene. 2000 Jan 4;241(1):75-85.
PMID 10607901
 
Hyperphosphorylation by cyclin B/CDK1 in mitosis resets CUX1 DNA binding clock at each cell cycle.
Sansregret L, Gallo D, Santaguida M, Leduy L, Harada R, Nepveu A.
J Biol Chem. 2010 Oct 22;285(43):32834-43. Epub 2010 Aug 19.
PMID 20729212
 
Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2).
Santaguida M, Ding Q, Berube G, Truscott M, Whyte P, Nepveu A.
J Biol Chem. 2001 Dec 7;276(49):45780-90. Epub 2001 Oct 2.
PMID 11584018
 
Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids.
Scherer SW, Neufeld EJ, Lievens PM, Orkin SH, Kim J, Tsui LC.
Genomics. 1993 Mar;15(3):695-6.
PMID 8468066
 
Nuclear matrix attachment regions of human papillomavirus type 16 repress or activate the E6 promoter, depending on the physical state of the viral DNA.
Stunkel W, Huang Z, Tan SH, O'Connor MJ, Bernard HU.
J Virol. 2000 Mar;74(6):2489-501.
PMID 10684263
 
Novel CUX1 missense mutation in association with 7q- at leukemic transformation of MPN.
Thoennissen NH, Lasho T, Thoennissen GB, Ogawa S, Tefferi A, Koeffler HP.
Am J Hematol. 2011 Aug;86(8):703-5. doi: 10.1002/ajh.22069. Epub 2011 Jun 14.
PMID 21674579
 
Carboxyl-terminal proteolytic processing of CUX1 by a caspase enables transcriptional activation in proliferating cells.
Truscott M, Denault JB, Goulet B, Leduy L, Salvesen GS, Nepveu A.
J Biol Chem. 2007 Oct 12;282(41):30216-26. Epub 2007 Aug 6.
PMID 17681953
 
Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements.
Tsutsumi S, Taketani T, Nishimura K, Ge X, Taki T, Sugita K, Ishii E, Hanada R, Ohki M, Aburatani H, Hayashi Y.
Cancer Res. 2003 Aug 15;63(16):4882-7.
PMID 12941810
 
CCAAT displacement protein regulates nuclear factor-kappa beta-mediated chemokine transcription in melanoma cells.
Ueda Y, Su Y, Richmond A.
Melanoma Res. 2007 Apr;17(2):91-103.
PMID 17496784
 
The mouse homeodomain protein Phox2 regulates Ncam promoter activity in concert with Cux/CDP and is a putative determinant of neurotransmitter phenotype.
Valarche I, Tissier-Seta JP, Hirsch MR, Martinez S, Goridis C, Brunet JF.
Development. 1993 Nov;119(3):881-96.
PMID 7910552
 
Expression of a cut-related homeobox gene in developing and polycystic mouse kidney.
Vanden Heuvel GB, Bodmer R, McConnell KR, Nagami GT, Igarashi P.
Kidney Int. 1996 Aug;50(2):453-61.
PMID 8840273
 
The CCAAT displacement protein/cut homeodomain protein represses osteocalcin gene transcription and forms complexes with the retinoblastoma protein-related protein p107 and cyclin A.
van Gurp MF, Pratap J, Luong M, Javed A, Hoffmann H, Giordano A, Stein JL, Neufeld EJ, Lian JB, Stein GS, van Wijnen AJ.
Cancer Res. 1999 Dec 1;59(23):5980-8.
PMID 10606245
 

Citation

This paper should be referenced as such :
Kè_hnemuth, B ; Michl, P
CUX1 (cut-like homeobox 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(3):191-195.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CUX1ID403ch7q22.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(7;15)(q22;q14) CUX1/NUTM1 a novel fusion


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Uterus: Leiomyoma


External links

Nomenclature
HGNC (Hugo)CUX1   2557
Cards
AtlasCUX1ID403ch7q22
Entrez_Gene (NCBI)CUX1  1523  cut like homeobox 1
AliasesCASP; CDP; CDP/Cut; CDP1; 
COY1; CUTL1; CUX; Clox; Cux/CDP; GOLIM6; Nbla10317; p100; p110; p200; p75
GeneCards (Weizmann)CUX1
Ensembl hg19 (Hinxton)ENSG00000257923 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000257923 [Gene_View]  chr7:101815904-102258233 [Contig_View]  CUX1 [Vega]
ICGC DataPortalENSG00000257923
TCGA cBioPortalCUX1
AceView (NCBI)CUX1
Genatlas (Paris)CUX1
WikiGenes1523
SOURCE (Princeton)CUX1
Genetics Home Reference (NIH)CUX1
Genomic and cartography
GoldenPath hg38 (UCSC)CUX1  -     chr7:101815904-102258233 +  7q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CUX1  -     7q22.1   [Description]    (hg19-Feb_2009)
EnsemblCUX1 - 7q22.1 [CytoView hg19]  CUX1 - 7q22.1 [CytoView hg38]
Mapping of homologs : NCBICUX1 [Mapview hg19]  CUX1 [Mapview hg38]
OMIM116896   
Gene and transcription
Genbank (Entrez)AB075522 AK056307 AK122726 AK125097 AK222832
RefSeq transcript (Entrez)NM_001202543 NM_001202544 NM_001202545 NM_001202546 NM_001913 NM_181500 NM_181552
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CUX1
Cluster EST : UnigeneHs.191482 [ NCBI ]
CGAP (NCI)Hs.191482
Alternative Splicing GalleryENSG00000257923
Gene ExpressionCUX1 [ NCBI-GEO ]   CUX1 [ EBI - ARRAY_EXPRESS ]   CUX1 [ SEEK ]   CUX1 [ MEM ]
Gene Expression Viewer (FireBrowse)CUX1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1523
GTEX Portal (Tissue expression)CUX1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13948   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13948  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13948
Splice isoforms : SwissVarQ13948
PhosPhoSitePlusQ13948
Domains : Interpro (EBI)CASP_C   
Domain families : Pfam (Sanger)CASP_C (PF08172)   
Domain families : Pfam (NCBI)pfam08172   
Conserved Domain (NCBI)CUX1
DMDM Disease mutations1523
Blocks (Seattle)CUX1
SuperfamilyQ13948
Human Protein AtlasENSG00000257923
Peptide AtlasQ13948
HPRD00295
IPIIPI00026673   IPI00472247   IPI00419894   IPI00736943   IPI00742111   IPI00741668   IPI00071696   IPI00926621   IPI00956257   IPI00982754   IPI00979706   IPI00927318   
Protein Interaction databases
DIP (DOE-UCLA)Q13948
IntAct (EBI)Q13948
FunCoupENSG00000257923
BioGRIDCUX1
STRING (EMBL)CUX1
ZODIACCUX1
Ontologies - Pathways
QuickGOQ13948
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  Golgi membrane  retrograde transport, vesicle recycling within Golgi  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  protein tyrosine kinase activity  nucleus  nucleoplasm  Golgi apparatus  cytosol  transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  multicellular organism development  peptidyl-tyrosine phosphorylation  protein binding, bridging  sequence-specific DNA binding  Golgi vesicle transport  positive regulation of dendrite morphogenesis  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  Golgi membrane  retrograde transport, vesicle recycling within Golgi  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  protein tyrosine kinase activity  nucleus  nucleoplasm  Golgi apparatus  cytosol  transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  multicellular organism development  peptidyl-tyrosine phosphorylation  protein binding, bridging  sequence-specific DNA binding  Golgi vesicle transport  positive regulation of dendrite morphogenesis  
REACTOMEQ13948 [protein]
REACTOME PathwaysR-HSA-6811438 [pathway]   
NDEx NetworkCUX1
Atlas of Cancer Signalling NetworkCUX1
Wikipedia pathwaysCUX1
Orthology - Evolution
OrthoDB1523
GeneTree (enSembl)ENSG00000257923
Phylogenetic Trees/Animal Genes : TreeFamCUX1
HOVERGENQ13948
HOGENOMQ13948
Homologs : HomoloGeneCUX1
Homology/Alignments : Family Browser (UCSC)CUX1
Gene fusions - Rearrangements
Fusion : MitelmanCUX1/AGR3 [7q22.1/7p21.1]  
Fusion : MitelmanCUX1/AHCYL2 [7q22.1/7q32.1]  [t(7;7)(q22;q32)]  
Fusion : MitelmanCUX1/EHBP1L1 [7q22.1/11q13.1]  [t(7;11)(q22;q13)]  
Fusion : MitelmanCUX1/FGFR1 [7q22.1/8p11.23]  [t(7;8)(q22;p11)]  
Fusion : MitelmanCUX1/MARCH10 [7q22.1/17q23.2]  [t(7;17)(q22;q23)]  
Fusion : MitelmanCUX1/THSD7A [7q22.1/7p21.3]  [t(7;7)(p21;q22)]  
Fusion : MitelmanMAP2K1/CUX1 [15q22.31/7q22.1]  [t(7;15)(q22;q22)]  
Fusion : MitelmanORAI2/CUX1 [7q22.1/7q22.1]  [t(7;7)(q22;q22)]  
Fusion: TCGACUX1 7q22.1 AHCYL2 7q32.1 LUSC
Fusion: TCGACUX1 7q22.1 EHBP1L1 11q13.1 LUSC
Fusion: TCGACUX1 7q22.1 MARCH10 17q23.2 BRCA
Fusion: TCGACUX1 7q22.1 THSD7A 7p21.3 HNSC
Fusion: TCGAMAP2K1 15q22.31 CUX1 7q22.1 KIRC
Fusion: TCGAORAI2 7q22.1 CUX1 7q22.1 LGG
Fusion : TICdbCUX1 [7q22.1]  -  AGR3 [7p21.1]
Fusion Cancer (Beijing)RPL41 [12q13.2]  -  CUX1 [7q22.1]  [FUSC001019]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCUX1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CUX1
dbVarCUX1
ClinVarCUX1
1000_GenomesCUX1 
Exome Variant ServerCUX1
ExAC (Exome Aggregation Consortium)CUX1 (select the gene name)
Genetic variants : HAPMAP1523
Genomic Variants (DGV)CUX1 [DGVbeta]
DECIPHERCUX1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCUX1 
Mutations
ICGC Data PortalCUX1 
TCGA Data PortalCUX1 
Broad Tumor PortalCUX1
OASIS PortalCUX1 [ Somatic mutations - Copy number]
Cancer Gene: CensusCUX1 
Somatic Mutations in Cancer : COSMICCUX1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCUX1
intOGen PortalCUX1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CUX1
DgiDB (Drug Gene Interaction Database)CUX1
DoCM (Curated mutations)CUX1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CUX1 (select a term)
intoGenCUX1
NCG5 (London)CUX1
Cancer3DCUX1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM116896   
Orphanet
MedgenCUX1
Genetic Testing Registry CUX1
NextProtQ13948 [Medical]
TSGene1523
GENETestsCUX1
Target ValidationCUX1
Huge Navigator CUX1 [HugePedia]
snp3D : Map Gene to Disease1523
BioCentury BCIQCUX1
ClinGenCUX1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1523
Chemical/Pharm GKB GenePA162382924
Clinical trialCUX1
Miscellaneous
canSAR (ICR)CUX1 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=CUX1
Probes
Litterature
PubMed97 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCUX1
EVEXCUX1
GoPubMedCUX1
iHOPCUX1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:08:37 CEST 2017

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