Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolyticenzyme 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]
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-mycprotooncogene.[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]
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.
CagA protein was found to activate ENO1 expression through activating the Src and MEK/ERKpathways as a mechanism for H. pylori-mediated gastric diseases.[14]
Hemolytic anemia
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.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
^ abcdefghZhu X, Miao X, Wu Y, Li C, Guo Y, Liu Y, Chen Y, Lu X, Wang Y, He S (July 2015). "ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in non-Hodgkin lymphomas". Experimental Cell Research. 335 (2): 216–23. doi:10.1016/j.yexcr.2015.05.020. PMID26024773.
^Kim AY, Lim B, Choi J, Kim J (October 2016). "The TFG-TEC oncoprotein induces transcriptional activation of the human β-enolase gene via chromatin modification of the promoter region". Molecular Carcinogenesis. 55 (10): 1411–23. doi:10.1002/mc.22384. PMID26310886. S2CID25167240.
^Moore TL, Gillian BE, Crespo-Pagnussat S, Feller L, Chauhan AK (2014). "Measurement and evaluation of isotypes of anti-citrullinated fibrinogen and anti-citrullinated alpha-enolase antibodies in juvenile idiopathic arthritis". Clinical and Experimental Rheumatology. 32 (5): 740–6. PMID25068682.
^Yoneda M, Fujii A, Ito A, Yokoyama H, Nakagawa H, Kuriyama M (April 2007). "High prevalence of serum autoantibodies against the amino terminal of alpha-enolase in Hashimoto's encephalopathy". Journal of Neuroimmunology. 185 (1–2): 195–200. doi:10.1016/j.jneuroim.2007.01.018. PMID17335908. S2CID11857420.
^Nahm DH, Lee KH, Shin JY, Ye YM, Kang Y, Park HS (August 2006). "Identification of alpha-enolase as an autoantigen associated with severe asthma". The Journal of Allergy and Clinical Immunology. 118 (2): 376–81. doi:10.1016/j.jaci.2006.04.002. PMID16890761.
^Lee KH, Chung HS, Kim HS, Oh SH, Ha MK, Baik JH, Lee S, Bang D (July 2003). "Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease". Arthritis and Rheumatism. 48 (7): 2025–35. doi:10.1002/art.11074. PMID12847697.
^Nielsen K, Vorum H, Fagerholm P, Birkenkamp-Demtröder K, Honoré B, Ehlers N, Orntoft TF (February 2006). "Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study". Experimental Eye Research. 82 (2): 201–9. doi:10.1016/j.exer.2005.06.009. PMID16083875.
^Stefanini M (1972). "Chronic hemolytic anemia associated with erythrocyte enolase deficiency exacerbated by ingestion of nitrofurantoin". American Journal of Clinical Pathology. 58 (4): 408–14. doi:10.1093/ajcp/58.5.408. PMID4640298.
