ENO1 gene product binds to the c-myc promoter and acts as a transcriptional repressor: relationship with Myc promoter-binding protein 1 (MBP-1).
The Myc promoter-binding protein-1 (MBP-1) is a 37-38 kDa protein that binds to the c-myc P2 promoter and negatively regulates transcription of the protooncogene. MBP-1 cDNA shares 97% similarity with the cDNA encoding the glycolytic enzyme alpha-enolase and both genes have been mapped to the same region of human chromosome 1, suggesting the hypothesis that the two proteins might be encoded by the same gene. We show here data indicating that a 37 kDa protein is alternatively translated from the full-length alpha-enolase mRNA. This shorter form of alpha-enolase is able to bind the MBP-1 consensus sequence and to downregulate expression of a luciferase reporter gene under the control of the c-myc P2 promoter. Furthermore, using alpha-enolase/green fluorescent protein chimeras in transfection experiments we show that, while the 48 kDa alpha-enolase mainly has a cytoplasmic localization, the 37 kDa alpha-enolase is preferentially localized in the cell nuclei. The finding that a transcriptional repressor of the c-myc oncogene is an alternatively translated product of the ENO1 gene, which maps to a region of human chromosome 1 frequently deleted in human cancers, makes ENO1 a potential candidate for tumor suppressor.
Feo
S
S
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle Scienze, Parco D'Orleans, 90128, Palermo, Italy. feo@unipa.it
Arcuri
D
D
Piddini
E
E
Passantino
R
R
Giallongo
A
A
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D014408:Biomarkers, Tumor; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018387:Codon, Initiator; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase