MBP-1 is efficiently encoded by an alternative transcript of the ENO1 gene but post-translationally regulated by proteasome-dependent protein turnover

Jrhau Lung, Ko Jiunn Liu, Jang Yang Chang, Sy Jye Leu, Neng Yao Shih

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The c-myc promoter-binding protein-1 (MBP-1) is a transcriptional suppressor of tumorigenesis and thought to be the product of alternative translation initiation of the -enolase (ENO1) transcript. In the present study, we cloned a 2552-bp novel cDNA with a putative coding sequence of MBP-1 and functionally examined its ability to encode the MBP-1 protein. Similarly to ENO1, the obtained MBP-1 was widely and differentially expressed in a variety of normal tissues and cancer cells. Experiments using MBP-1 promoter-driven luciferase reporter assays, biochemical cell fractionation followed by RT-PCR detection of the cytoplasmic mRNA, and transcriptiontranslation-coupled reactions, consistently demonstrated that this novel transcript was alternatively transcribed from intron III of the ENO1 gene and was feasible for MBP-1 production. Hypoxia treatments significantly increased the transcriptional activation of the MBP-1 gene. Blocking the proteasomal degradation by MG132 stabilized the MBP-1 protein in cells. Compared with the translation efficiency for production of the MBP-1 protein, the MBP-1 transcript was 17.8 times more efficient than the ENO1 transcript. Thus, we suggest that this newly discovered transcript is a genuine template for the protein synthesis of MBP-1 in cells, and optimal expression of this gene in tumors may lead to effective clinical therapies for cancers.

Original languageEnglish
Pages (from-to)4308-4321
Number of pages14
JournalFEBS Journal
Volume277
Issue number20
DOIs
Publication statusPublished - 2010

Fingerprint

Proteasome Endopeptidase Complex
Carrier Proteins
Genes
Proteins
Cell Fractionation
Neoplasms
Phosphopyruvate Hydratase
Fractionation
Luciferases
Introns
Transcriptional Activation
Tumors
Assays
Carcinogenesis
Complementary DNA
Chemical activation
Cells
Tissue
Gene Expression
Degradation

Keywords

  • -enolase
  • alternative transcription initiation
  • c-myc promoter-binding protein-1
  • protein stability
  • ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

MBP-1 is efficiently encoded by an alternative transcript of the ENO1 gene but post-translationally regulated by proteasome-dependent protein turnover. / Lung, Jrhau; Liu, Ko Jiunn; Chang, Jang Yang; Leu, Sy Jye; Shih, Neng Yao.

In: FEBS Journal, Vol. 277, No. 20, 2010, p. 4308-4321.

Research output: Contribution to journalArticle

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