Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structural lens protein ( tau- crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy. [5]
ENO1 is one of three enolase isoforms, the other two being ENO2 (ENO-γ) and ENO3 (ENO-β). [6] Each isoform is a protein subunit that can hetero- or homodimerize to form αα, αβ, αγ, ββ, and γγ dimers. [7] The ENO1 gene spans 18 kb and lacks a TATA box while possessing multiple transcription start sites. [8] A hypoxia-responsive element can be found in the ENO1 promoter and allows the enzyme to function in aerobic glycolysis and contribute to the Warburg effect in tumor cells. [9]
The mRNA transcript of the ENO1 gene can be alternatively translated into a cytoplasmic protein, with a molecular weight of 48 kDa, or a nuclear protein, with a molecular weight of a 37 kDa. [9] [10] The nuclear form was previously identified as Myc-binding protein-1 (MBP1), which downregulates the protein level of the c-myc protooncogene. [10] A start codon at codon 97 of ENO1 and a Kozak consensus sequence were found preceding the 3' region of ENO1 encoding the MBP1 protein. In addition, the N-terminal region of the MBP1 protein it critical to DNA binding and, thus, its inhibitory function. [10]
As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. [6] [9] [11] This isozyme is ubiquitously expressed in adult human tissues, including liver, brain, kidney, and spleen. [6] Within cells, ENO1 predominantly localizes to the cytoplasm, though an alternatively translated form is localized to the nucleus. [6] [9] Its nuclear form, also known as MBP1, functions solely as a tumor suppressor by binding and inhibiting the c-myc protooncogene promoter, and lacks the glycolytic enzyme activity of the cytoplasmic form. [10] ENO1 also plays a role in other functions, including a cell surface receptor for plasminogen on pathogens, such as streptococci, and activated immune cells, leading to systemic infection or tissue invasion; an oxidative stress protein in endothelial cells; a lens crystalline; a heat shock protein; and a binding partner of cytoskeletal and chromatin structures to aid in transcription. [9] [10] [11] [12] [13]
ENO1 overexpression has been associated with multiple tumors, including glioma, neuroendocrine tumors, neuroblastoma, pancreatic cancer, prostate cancer, cholangiocarcinoma, thyroid carcinoma, lung cancer, hepatocellular carcinoma, and breast cancer. [6] [9] [13] [14] In many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/ AKT signaling pathway and induced tumorigenesis by activating plasminogen. [6] [9] Moreover, ENO1 is expressed on the tumor cell surface during pathological conditions such as inflammation, autoimmunity, and malignancy. Its role as a plasminogen receptor leads to extracellular matrix degradation and cancer invasion. [9] [13] [14] Due to its surface expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional. [9] Moreover, in tumors such as non-Hodgkin lymphomas (NHLs) and breast cancer, inhibition of ENO1 expression decreased tolerance to hypoxia while increasing sensitivity to radiation therapy, thus indicating that ENO1 may have aided chemoresistance. [6] [11] Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients. [6] [11] [13]
ENO1 is located on the 1p36 tumor suppressor locus near MIR34A which is homozygously deleted in Glioblastoma, Hepatocellular carcinoma and Cholangiocarcinoma. [15] [16] The co-deletion of ENO1 is a passenger event with the resultant tumor cells being entirely dependent on ENO2 for the execution of glycolysis. [17] [18] Tumor cells with such deletions are exceptionally sensitive towards ablation of ENO2. [17] [18] Inhibition of ENO2 in ENO1-homozygously deleted cancer cells constitutes an example of synthetic lethality treatment for cancer.
ENO1 has been detected in serum drawn from children diagnosed with juvenile idiopathic arthritis. [19]
Alpha-enolase has been identified as an autoantigen in Hashimoto's encephalopathy. [20] Single studies have also identified it as an autoantigen associated with severe asthma [21] and a putative target antigen of anti-endothelial cell antibody in Behçet's disease. [22] Reduced expression of the enzyme has been found in the corneal epithelium of people suffering from keratoconus. [23] [24]
CagA protein was found to activate ENO1 expression through activating the Src and MEK/ ERK pathways as a mechanism for H. pylori-mediated gastric diseases. [14]
Enolase deficiency is a rare inborn error of metabolism disease, leads to hemolytic anemia in affected homozygous carriers of loss of function mutations in ENO1. [25] As with other glycolysis enzyme deficiency diseases, the condition is aggravated by redox-cycling agents such as nitrofurantoin.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Alpha-enolase has been shown to interact with TRAPPC2. [26]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Aliases | ENO1, ENO1L1, MPB1, NNE, PPH, HEL-S-17, enolase 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 172430 MGI: 95393 HomoloGene: 134343 GeneCards: ENO1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structural lens protein ( tau- crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy. [5]
ENO1 is one of three enolase isoforms, the other two being ENO2 (ENO-γ) and ENO3 (ENO-β). [6] Each isoform is a protein subunit that can hetero- or homodimerize to form αα, αβ, αγ, ββ, and γγ dimers. [7] The ENO1 gene spans 18 kb and lacks a TATA box while possessing multiple transcription start sites. [8] A hypoxia-responsive element can be found in the ENO1 promoter and allows the enzyme to function in aerobic glycolysis and contribute to the Warburg effect in tumor cells. [9]
The mRNA transcript of the ENO1 gene can be alternatively translated into a cytoplasmic protein, with a molecular weight of 48 kDa, or a nuclear protein, with a molecular weight of a 37 kDa. [9] [10] The nuclear form was previously identified as Myc-binding protein-1 (MBP1), which downregulates the protein level of the c-myc protooncogene. [10] A start codon at codon 97 of ENO1 and a Kozak consensus sequence were found preceding the 3' region of ENO1 encoding the MBP1 protein. In addition, the N-terminal region of the MBP1 protein it critical to DNA binding and, thus, its inhibitory function. [10]
As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. [6] [9] [11] This isozyme is ubiquitously expressed in adult human tissues, including liver, brain, kidney, and spleen. [6] Within cells, ENO1 predominantly localizes to the cytoplasm, though an alternatively translated form is localized to the nucleus. [6] [9] Its nuclear form, also known as MBP1, functions solely as a tumor suppressor by binding and inhibiting the c-myc protooncogene promoter, and lacks the glycolytic enzyme activity of the cytoplasmic form. [10] ENO1 also plays a role in other functions, including a cell surface receptor for plasminogen on pathogens, such as streptococci, and activated immune cells, leading to systemic infection or tissue invasion; an oxidative stress protein in endothelial cells; a lens crystalline; a heat shock protein; and a binding partner of cytoskeletal and chromatin structures to aid in transcription. [9] [10] [11] [12] [13]
ENO1 overexpression has been associated with multiple tumors, including glioma, neuroendocrine tumors, neuroblastoma, pancreatic cancer, prostate cancer, cholangiocarcinoma, thyroid carcinoma, lung cancer, hepatocellular carcinoma, and breast cancer. [6] [9] [13] [14] In many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/ AKT signaling pathway and induced tumorigenesis by activating plasminogen. [6] [9] Moreover, ENO1 is expressed on the tumor cell surface during pathological conditions such as inflammation, autoimmunity, and malignancy. Its role as a plasminogen receptor leads to extracellular matrix degradation and cancer invasion. [9] [13] [14] Due to its surface expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional. [9] Moreover, in tumors such as non-Hodgkin lymphomas (NHLs) and breast cancer, inhibition of ENO1 expression decreased tolerance to hypoxia while increasing sensitivity to radiation therapy, thus indicating that ENO1 may have aided chemoresistance. [6] [11] Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients. [6] [11] [13]
ENO1 is located on the 1p36 tumor suppressor locus near MIR34A which is homozygously deleted in Glioblastoma, Hepatocellular carcinoma and Cholangiocarcinoma. [15] [16] The co-deletion of ENO1 is a passenger event with the resultant tumor cells being entirely dependent on ENO2 for the execution of glycolysis. [17] [18] Tumor cells with such deletions are exceptionally sensitive towards ablation of ENO2. [17] [18] Inhibition of ENO2 in ENO1-homozygously deleted cancer cells constitutes an example of synthetic lethality treatment for cancer.
ENO1 has been detected in serum drawn from children diagnosed with juvenile idiopathic arthritis. [19]
Alpha-enolase has been identified as an autoantigen in Hashimoto's encephalopathy. [20] Single studies have also identified it as an autoantigen associated with severe asthma [21] and a putative target antigen of anti-endothelial cell antibody in Behçet's disease. [22] Reduced expression of the enzyme has been found in the corneal epithelium of people suffering from keratoconus. [23] [24]
CagA protein was found to activate ENO1 expression through activating the Src and MEK/ ERK pathways as a mechanism for H. pylori-mediated gastric diseases. [14]
Enolase deficiency is a rare inborn error of metabolism disease, leads to hemolytic anemia in affected homozygous carriers of loss of function mutations in ENO1. [25] As with other glycolysis enzyme deficiency diseases, the condition is aggravated by redox-cycling agents such as nitrofurantoin.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Alpha-enolase has been shown to interact with TRAPPC2. [26]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.