DNASE1L1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | DNASE1L1 , DNAS1L1, DNASEX, DNL1L, G4.8, XIB, deoxyribonuclease I-like 1, deoxyribonuclease 1 like 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 300081 MGI: 109628 HomoloGene: 4896 GeneCards: DNASE1L1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Deoxyribonuclease-1-like 1 is an enzyme that in humans is encoded by the DNASE1L1 gene. [5] [6] [7] It is also known as DNaseX due to its localisation on the X chromosome . [8]
This gene encodes a member of the deoxyribonuclease family and the protein and DNA shows high sequence similarity to lysosomal DNase I. Alternate transcriptional splice variants, encoding the same protein, have been characterized. [7]
The DNase1L1/DNaseX gene was discovered in the early 1990s by Johannes F. Coy as a member of the Molecular Genome Analysis research project at the DKFZ (German Cancer Research Center) in Heidelberg and first published in 1996. [8] [9]
Just like the DNase I enzyme produced by the DNase I gene, the DNase1L1 (DNaseX) enzyme produced by the DNase1L1 (DNaseX) gene cuts double-stranded deoxyribonucleic acid (DNA) molecular chains into pieces. The cutting of DNA into 300-base pair pieces represents the final step in the execution of programmed cell death (apoptosis). Cells can then no longer perform cell division and thus cannot develop into tumor cells. DNase I and DNase1L1 (DNaseX) carry out programmed cell death (apoptosis) and thus protect the human body from the development of tumor cells. Conversely, the absence of DNase enzyme activity leads to the increased formation of tumor cells, as the execution of apoptosis is prevented. [10] [11]
A fundamental common feature of all tumors is the disruption of apoptosis. Degenerated cells thus evade self-destruction, continue to grow and carry the risk of further degeneration through further mutations and increase in aggressiveness and malignancy. [12]
DNaseX (DNase1L1) has a special feature that makes it suitable as a marker for the detection of cancer. The concentration of the DNaseX enzyme increases in tumor cells - in contrast to other DNases, whose concentration decreases in the course of tumor development. [13]
DNaseX is generally produced in greater quantities in tumor cells in order to induce the desired programmed cell death. However, by synthesizing specific inhibitors, the tumor cell can suppress the enzyme activity of DNaseX and thus prevent the final apoptosis step, the DNA cutting. [12]
The accumulation of DNaseX has been detected in all premalignant and malignant tumor types examined to date. The accumulation in cells occurs when DNaseX cannot fulfill its task. Then the cell continues to produce the DNaseX protein because it wants to induce apoptosis. This situation leads to higher and higher concentrations of DNaseX in the cell. If a DNaseX overproduction can be detected, this can be taken as an indicator of impaired apoptosis and as an indication of the development of tumors in the body. [14] [15] [16]
The Apo10 epitope plays a special role in this process. This characteristic section of the protein sequence of the DNaseX enzyme can be identified diagnostically using the same-named monoclonal antibody Apo10 (DJ28D4). [16] [17] [18] [19]
The resulting accumulation of DNaseX (Apo10) in the nucleus also makes the detection easier - since the amount of Apo10 in the nucleus increases sharply.
DNaseX (Apo10) is already applied in diagnostic cancer screening. The enzymes DNaseX (Apo10) and TKTL1 are detected in PanTum Detect, a blood test used in combination with imaging techniques such as MRI and PET-CT for the early detection of cancer. [20] The detection of DNaseX (Apo10) and TKTL1 in immune cells using EDIM technology provides clues to possible tumor disease. [15] [21] In case of an abnormal result, clarification by imaging techniques is recommended. [20]
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day.
Deoxyribonuclease refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in cells includes breaking down extracellular DNA (ecDNA) excreted by apoptosis, necrosis, and neutrophil extracellular traps (NET) of cells to help reduce inflammatory responses that otherwise are elicited. A wide variety of deoxyribonucleases are known and fall into one of two families, which differ in their substrate specificities, chemical mechanisms, and biological functions. Laboratory applications of DNase include purifying proteins when extracted from prokaryotic organisms. Additionally, DNase has been applied as a treatment for diseases that are caused by ecDNA in the blood plasma. Assays of DNase are emerging in the research field as well.
In the field of genetics, a suicide gene is a gene that will cause a cell to kill itself through the process of apoptosis. Activation of a suicide gene can cause death through a variety of pathways, but one important cellular "switch" to induce apoptosis is the p53 protein. Stimulation or introduction of suicide genes is a potential way of treating cancer or other proliferative diseases.
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno", in reference to antibodies used in the procedure, and "histo", meaning tissue. Albert Coons conceptualized and first implemented the procedure in 1941.
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.
In the field of cell biology, TNF-related apoptosis-inducing ligand (TRAIL), is a protein functioning as a ligand that induces the process of cell death called apoptosis.
Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ANG gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular RNA, resulting in modulated levels of protein synthesis and interacts with DNA causing a promoter-like increase in the expression of rRNA. Ang is associated with cancer and neurological disease through angiogenesis and through activating gene expression that suppresses apoptosis.
Deoxyribonuclease I, is an endonuclease of the DNase family coded by the human gene DNASE1. DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding 5'-phosphate-terminated polynucleotides with a free hydroxyl group on position 3', on average producing tetranucleotides. It acts on single-stranded DNA, double-stranded DNA, and chromatin. In addition to its role as a waste-management endonuclease, it has been suggested to be one of the deoxyribonucleases responsible for DNA fragmentation during apoptosis.
Deoxyribonuclease II is an endonuclease that hydrolyzes phosphodiester linkages of deoxyribonucleotide in native and denatured DNA, yielding products with 3'-phosphates and 5'-hydroxyl ends, which occurs as a result of single-strand cleaving mechanism. As the name implies, it functions optimally at acid pH because it is commonly found in low pH environment of lysosomes.
The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.
Deoxyribonuclease IV (phage-T4-induced) is catalyzes the degradation nucleotides in DsDNA by attacking the 5'-terminal end.
Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.
Decoy receptor 2 (DCR2), also known as TRAIL receptor 4 (TRAILR4) and tumor necrosis factor receptor superfamily member 10D (TNFRSF10D), is a human cell surface receptor of the TNF-receptor superfamily.
Deoxyribonuclease gamma is an enzyme that in humans is encoded by the DNASE1L3 gene.
Transketolase-like-1 (TKTL1) is a gene closely related to the transketolase gene (TKT). It emerged in mammals during the course of evolution and, according to the latest research findings, is considered one of the key genes that distinguishes modern humans from Neanderthals.
Deoxyribonuclease-1-like 2 is an enzyme that in humans is encoded by the DNASE1L2 gene.
Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. It breaks up the DNA during apoptosis and promotes cell differentiation. It is usually an inactive monomer inhibited by ICAD. This is cleaved before dimerization.
ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.
Epitope Detection in Monocytes (EDIM) is a technology that uses the innate immune system's mechanisms to detect biomarkers or antigens in immune cells. It is a non-invasive form of liquid biopsy, i.e. biopsy from blood, which analyzes activated macrophages (CD14+/CD16+) for disease-specific epitopes, such as tumor cell components.