Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''CUX1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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. 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.

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 The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...

reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor,

PIK3IP1 Phosphoinositide-3-kinase-interacting protein 1 is an enzyme that in humans is encoded by the ''PIK3IP1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." m ...

(phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

phosphoinositide 3-kinase Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

(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.

CASP

Tne CUX1 gene Alternatively Spliced Product was first reported in 1997. The CUX1 gene has up to 33

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s. CASP

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

includes exons 1 through 14 and 25 through 33. The human CASP protein is predicted to contain 678

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

, of which 400 are shared with CUTL1. CASP protein is approximately 80 k D. It lacks the DNA binding region of CUTL1, but instead contains a trans-membrane domain that allows it to insert into lipid bilayers. It has been localized to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

. CASP has been reported to be part of a complex with Golgin 84 that tethers

COPI COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the ''cis'' end of the Golgi complex The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most ...

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

and is important for retrograde transport in the Golgi and between the Golgi and

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

. The targeting of vesicles involves tethers and

SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle fu ...

Interactions

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

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

CREB binding protein Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrin ...

, *

Retinoblastoma protein The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...

, and *

SATB1 SATB1 (special AT-rich sequence-binding protein-1) is a protein which in humans is encoded by the ''SATB1'' gene. Function SATB1, the global chromatin organizer and transcription factor, has emerged as a key factor integrating higher-order chro ...

These physical interactions are reported in

BioPlex BioPlex (biophysical interactions of ORFeome-based complexes) is an open access resource for studying protein-protein interactions. It is the result of collaborations between Harvard Medical School and Biogen. BioPlex 1.0 reported 23,744 interact ...

2.0 *

MAGEA10 ''MAGEA10'' (MAGE family member A10) is a protein-coding gene in humans clustered at chromosomal location Xq28. Function This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identi ...

EXT2 The ext2 or second extended file system is a file system for the Linux kernel. It was initially designed by French software developer Rémy Card as a replacement for the extended file system (ext). Having been designed according to the same pr ...

RAB30 RAB30, member RAS oncogene family is a protein that in humans is encoded by the RAB30 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation ...

HLA-DQA1 Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of tw ...

STX6 Syntaxin-6 is a protein that in humans is encoded by the ''STX6'' gene. Interactions STX6 has been shown to interact with SNAP23, VAMP3 and VAMP4. N terminal protein domain The protein domain Syntaxin 6 N terminal protein domain is a solubl ...

WDR83 WD repeat domain 83 is a protein that in humans is encoded by the WDR83 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth ...

SLC39A4 Zinc transporter ZIP4 is a transmembrane protein which in humans is encoded by the ''SLC39A4'' gene. It is associated with acrodermatitis enteropathica Acrodermatitis enteropathica is an autosomal recessive metabolic disorder affecting the uptak ...

LAMP1 Lysosomal-associated membrane protein 1 (LAMP-1) also known as lysosome-associated membrane glycoprotein 1 and CD107a (Cluster of Differentiation 107a), is a protein that in humans is encoded by the ''LAMP1'' gene. The human ''LAMP1'' gene is locat ...

POTEB POTE ankyrin domain family, member B is a protein in humans that is encoded by the ''POTEB'' gene.(Prostate, Ovary, Testes Expressed ankyrin domain family member B).It is most likely involved in mediating protein-protein interaction via its 5 a ...

SLC39A12 Solute carrier family 39 member 12 is a protein that in humans is encoded by the SLC39A12 gene. Function Zinc is an essential cofactor (biochemistry), cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, ...

Notes

References

External links

* * {{Transcription factors, g3 Transcription factors