CPNE1
Copine-1 is a protein that in humans is encoded by the CPNE1 gene.[5][6]
CPNE is a highly homologous protein first discovered in nematodes and plants. Nine CPNEs were originally discovered (CPNE1-9) and only 8 CPNEs were found in mammals (CPNE1-8). CPNE1-3 are the most widely distributed and are found in most mammalian tissues, this includes but is not limited to, the testis, kidney, brain, lung, heart, and intestine.[7] (CPNE-1) was reported in 1998, where it was identified by isolating annexin in Paramecium.[8]
CPNE-1 is a highly conservedCalcium-dependent membrane-binding proteins in different eukaryotes. In humans the CPNE1 gene encodes the, calcium dependant, Copine-1 protein which has an integrin A doman and two N-terminal type II C2 domains. Where the C2 domains act as calcium dependent phospholipid binding motifs and can be included in cell signaling or membrane trafficking pathways.[9] However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. CPNE-1 may also regulate molecular events at the interface of the cell membrane and cytoplasm. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Sequence analysis identified multiple alternatively spliced variants in the 5' UTR. All variants encode the same protein.[6]
Roles of CPNE1
CPNE1 has a general role in many biological processes, where it promotes the outgrowth of neurites by activating the AKT phosphorylation and plays an important role in the regulation of neural stem cell proliferation. New and old studies suggest that the important and dominant role of CPNE1 is in tumorigenesis and malignant progression.[10]
CPNE1 can regulate molecular events at the interface of the cell membrane and cytoplasm.[11] In brain cells, it is connected to the AKT signalling pathway, giving it importance in the neural stem cell functions in the course of brain development. Where it is detrimental in regulating the neural stem cell functions throughout the activation of the AKT-mTOR signalling pathway in the brain development phase.[12] It has an important role in the central nervous system as a regulator for neuronal differentiation of HiB5 cells. It does this by activating the AKT signalling pathway by its interactions with JAB-1 and 14-4-3 gamma (Kim et al., 2018). (The AKT Signaling pathway is a signal transduction pathway that helps the growth and survival in response to extracellular signals).
In addition to this role, CPNE1 has an important role in the presence and growth of different cancer types. Individuals with prostate cancer show a higher CPNE1 expression and this expression is affiliated with the stage and prognosis of patients with prostate cancer. This happens mechanistically when CPNE1 interacts with TRAF-2 (regulates a variety of different physiological roles, from inflammatory responses and T and B signalling to organogenesis and cell survival) To promote the progression of cancer.[13] In patients with osteosarcoma ( cancer that starts in the bone), CPNE1 has a role in increasing cell numbers and migration, it does this using the MAPK pathway (a pathway responsible for many pathological processes. All eukaryotic cells have multiple MAPK pathways that control gene expression, metabolism, survival, mitosis, motility, apoptosis, and differentiation. In addition to this there is the TGF-beta pathway (this pathway acts as a tumour suppressor, by mediating its anti-cell duplication effects in multiple different cell types).[14]
CPNE1 also has a role in promoting the progression of colorectal cancer and increases chemoresistance ( cancer affecting the colon or rectum, causing cells to grow out of control)[15] This happens due to the activation of the AKT-GLUT1/HK2 cascade (The AKT-glucose transporter 1-hexokinase2 pathway is responsible in regulating the glycolytic process in various cancer cells, due to colorectal cancer the AKT pathway increases the GLUT1 expression, CPNE1 activates the AKT to increase neuronal progenitor cell differentiation causing an implication in the regulation of the pathway.)[16]
In triple-negative breast cancer, CPNE1 increases tumorigenesis and radioresistance, due to the regulation of AKT activation. Due to this, it is possible to use the CPNE1 expression to sensitize the triple-negative breast cancer cells to therapy by radiation. In lung cancer, Non-Small Cell Lung Cancer (NSCLC) tissues have high demonstrations of CPNE1 which corresponds with lymph node metastasis (a serious condition in which the cancer invaded lymph nodes move to other organs) and less survival in patients.[17]
In hepatocellular carcinoma (HCC, is the most common type of primary liver cancer. It occurs in people with chronic liver diseases.) overexpressed CPNE1 is a regulator to the cell cycle process in order to mediate cell dedifferentiation.[18]
In gastric cancer (cancer that starts in the cells lining the stomach),[19] CPNE1 is upregulated (the process of increasing the response to a stimulus); This was identified using the Immunohistochemistry and Kaplan-Meier plotter database and the higher the CPNE1 the worse the prognosis. On the other hand, the proliferation of tumours can be suppressed, cell apoptosis can be accelerated and the cell cycle in vitro can enter arrest (in Vitro means in glass, it refers to tests, experiments, and medical procedures performed by researchers outside of living organisms) if the CPNE1 is silenced. In vivo experiments (in Vivo means within the living, it refers to tests, experiments, and medical procedures performed by researchers inside of living organisms).,[20] by using the Xenograft mouse model ( is a model based on the implantation of tumor cells from humans into mice that are immunocompromised in order to avoid graft versus host reaction of the mouse in opposition to the human tumor tissue [graft versus reaction is a systemic disorder that happens when the donated tissue cells think that the host is foreign and attacks the recipient's body cells],[21] tumor growth in vivo was found to be slowed down by the targeted inhibition of CPNE1. The specific inhibition of the DDIT3-FOS-MKNK2 axis has the ability to suppress the excessive cell duplication related to gastric cancer with the knockdown of CPNE1.[10] Overall, it is possible to use CPNE1 as a prognostic biomarker for cancers, however, they correlate with sex, age, cancer stage and tumour grade. Where an increased amount of CPNE1 leads to decreased survival chances and less CPNE1 leads to an increased chance of survival for the patient with cancer.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000214078 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000074643 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Creutz CE, Tomsig JL, Snyder SL, Gautier MC, Skouri F, Beisson J, Cohen J (January 1998). "The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans". The Journal of Biological Chemistry. 273 (3): 1393–1402. doi:10.1074/jbc.273.3.1393. PMID 9430674.
- ^ a b "Entrez Gene: CPNE1 copine I".
- ^ Tang H, Pang P, Qin Z, Zhao Z, Wu Q, Song S, Li F (2021). "The CPNE Family and Their Role in Cancers". Frontiers in Genetics. 12: 689097. doi:10.3389/fgene.2021.689097. PMC 8345009. PMID 34367247.
- ^ Tomsig JL, Creutz CE (December 2000). "Biochemical characterization of copine: a ubiquitous Ca2+-dependent, phospholipid-binding protein". Biochemistry. 39 (51): 16163–16175. doi:10.1021/bi0019949. PMID 11123945.
- ^ Tang H, Zhu J, Du W, Liu S, Zeng Y, Ding Z, et al. (July 2018). "CPNE1 is a target of miR-335-5p and plays an important role in the pathogenesis of non-small cell lung cancer". Journal of Experimental & Clinical Cancer Research. 37 (1): 131. doi:10.1186/s13046-018-0811-6. PMC 6029376. PMID 29970127.
- ^ a b Li Y, Li L, Liu H, Zhou T (October 2022). "CPNE1 silencing inhibits cell proliferation and accelerates apoptosis in human gastric cancer". European Journal of Pharmaceutical Sciences. 177: 106278. doi:10.1016/j.ejps.2022.106278. PMID 35985444. S2CID 251655274.
- ^ "CPNE1 copine 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
- ^ Kim TH, Sung SE, Cheal Yoo J, Park JY, Yi GS, Heo JY, et al. (January 2018). "Copine1 regulates neural stem cell functions during brain development". Biochemical and Biophysical Research Communications. 495 (1): 168–173. doi:10.1016/j.bbrc.2017.10.167. PMID 29101038.
- ^ Au PY, Yeh WC (2013). "Physiological Roles and Mechanisms of Signaling by TRAF2 and TRAF5". Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience.
- ^ Cargnello M, Roux PP (March 2011). "Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases". Microbiology and Molecular Biology Reviews. 75 (1): 50–83. doi:10.1128/MMBR.00031-10. PMC 3063353. PMID 21372320.
- ^ "What Is Colorectal Cancer? | CDC". www.cdc.gov. 23 February 2023.
- ^ Wang Y, Pan S, He X, Wang Y, Huang H, Chen J, et al. (27 January 2021). "CPNE1 Enhances Colorectal Cancer Cell Growth, Glycolysis, and Drug Resistance Through Regulating the AKT-GLUT1/HK2 Pathway". OncoTargets and Therapy. 14: 699–710. doi:10.2147/OTT.S284211. PMC 7850573. PMID 33536762.
- ^ "Cancer in Lymph Nodes May Help Tumors Metastasize - NCI". www.cancer.gov. 27 May 2022.
- ^ "Hepatocellular carcinoma - Overview". Mayo Clinic.
- ^ "What Is Stomach Cancer? - NCI". www.cancer.gov. 31 May 2023.
- ^ "In vivo vs. in vitro: What is the difference?". www.medicalnewstoday.com. 31 August 2020.
- ^ Justiz Vaillant AA, Modi P, Mohammadi O (2023). "Graft-Versus-Host Disease". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30855823.
Further reading
- Savino M, d'Apolito M, Centra M, van Beerendonk HM, Cleton-Jansen AM, Whitmore SA, et al. (October 1999). "Characterization of copine VII, a new member of the copine family, and its exclusion as a candidate in sporadic breast cancers with loss of heterozygosity at 16q24.3". Genomics. 61 (2): 219–226. doi:10.1006/geno.1999.5958. PMID 10534407.
- Tomsig JL, Snyder SL, Creutz CE (March 2003). "Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif". The Journal of Biological Chemistry. 278 (12): 10048–10054. doi:10.1074/jbc.M212632200. PMID 12522145.
- Cowland JB, Carter D, Bjerregaard MD, Johnsen AH, Borregaard N, Lollike K (September 2003). "Tissue expression of copines and isolation of copines I and III from the cytosol of human neutrophils". Journal of Leukocyte Biology. 74 (3): 379–388. doi:10.1189/jlb.0203083. PMID 12949241. S2CID 1754733.
- Tomsig JL, Sohma H, Creutz CE (March 2004). "Calcium-dependent regulation of tumour necrosis factor-alpha receptor signalling by copine". The Biochemical Journal. 378 (Pt 3): 1089–1094. doi:10.1042/BJ20031654. PMC 1224034. PMID 14674885.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (March 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233.
External links
- Human CPN1 genome location and CPN1 gene details page in the UCSC Genome Browser.
- Human CPNE1 genome location and CPNE1 gene details page in the UCSC Genome Browser.