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 bind s to the c-myc P2 promoter and negatively regulates transcription of the pr otooncogene, MBP-I cDNA shares 97% similarity with the cDNA encoding the gl ycolytic enzyme alpha-enolase and both genes have been mapped to the same r egion of human chromosome 1, suggesting the hypothesis that the two protein s might he encoded by the same gene. We shove here data indicating that a 3 7 kDa protein is alternatively translated from the full-length alpha-enolas e mRNA, This shorter form of alpha-enolase is able to bind the MBP-1 consen sus sequence and to downregulate expression of a luciferase reporter gene u nder the control of the c-myc P2 promoter. Furthermore, using alpha-enolase /green fluorescent protein chimeras in transfection experiments we show tha t, while the 48 kDa alpha-enolase mainly has a cytoplasmic localization, th e 37 kDa alpha-enolase is preferentially localized in the cell nuclei, The finding that a transcriptional repressor of the c-myc oncogene is an altern atively translated product of the ENO1 gene, which maps to a region of huma n chromosome I frequently deleted in human cancers, makes ENO1 a potential candidate for tumor suppressor. (C) 2000 Federation of European Biochemical Societies.