CUTL1
   HOME

TheInfoList



OR:

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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''CUX1''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


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 organisation, non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is l ...
reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor,
PIK3IP1 Phosphoinositide-3-kinase-interacting protein 1 (PIK3IP1) is an enzyme that in humans is encoded by the ''PIK3IP1'' gene. PIK3IP1 is a transmembrane protein that binds to PI3K, reducing signal to the PI3K/AKT/mTOR pathway. Through this mechanism ...
(phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
,
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

The 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 sequence ...
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 over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
, 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 Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
. 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 vesicle (biology), vesicles transporting proteins from the ''cis'' end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally Translation (genetics), synthesi ...
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 a neuron, synaptic vesicles (or neurotransmitter vesicles) s ...
and is important for retrograde transport in the Golgi and between the Golgi and
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
. The targeting of vesicles involves tethers and
SNARE SNARE proteins – "Soluble NSF attachment protein, SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells. The primary role of SNARE proteins is to m ...
s.


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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with: *
CREB binding protein CREB-binding protein, also known as CREBBP or CBP or KAT3A, (where CREB is cAMP response element-binding protein) is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrinsic acetyltransferase funct ...
, *
Retinoblastoma protein Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...
, and *
SATB1 SATB1 (special AT-rich sequence-binding protein-1) is a protein which in humans is encoded by the ''SATB1'' gene. It is a dimeric/tetrameric transcription factor with multiple DNA binding domains ( CUT1, CUT2 and a Homeobox domain). SATB1 spe ...
These physical interactions are reported in BioPlex 2.0 * MAGEA10 *
EXT2 ext2, or second extended file system, is a file system for the Linux kernel (operating system), kernel. It was initially designed by French software developer Rémy Card as a replacement for the extended file system (ext). Having been designed ...
* RAB30 *
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 ...
*
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 so ...
* WDR83 *
SLC39A4 Zinc transporter ZIP4 is a transmembrane protein which in humans is encoded by the ''SLC39A4'' gene. It is associated with acrodermatitis enteropathica. See also * Solute carrier family The solute carrier (SLC) group of membrane transport pro ...
*
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 loc ...
* POTEB * SLC39A12


Notes


References


Further reading

* * * * * * * * * * * * * * * *


External links

* * {{Transcription factors, g3 Transcription factors