摘要
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.
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 4308-4321 |
| 頁數 | 14 |
| 期刊 | FEBS Journal |
| 卷 | 277 |
| 發行號 | 20 |
| DOIs | |
| 出版狀態 | 已發佈 - 2010 |
指紋
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Medicine(all)
引用此文
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.
於: FEBS Journal, 卷 277, 編號 20, 2010, p. 4308-4321.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - MBP-1 is efficiently encoded by an alternative transcript of the ENO1 gene but post-translationally regulated by proteasome-dependent protein turnover
AU - Lung, Jrhau
AU - Liu, Ko Jiunn
AU - Chang, Jang Yang
AU - Leu, Sy Jye
AU - Shih, Neng Yao
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - -enolase
KW - alternative transcription initiation
KW - c-myc promoter-binding protein-1
KW - protein stability
KW - ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=77957282695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957282695&partnerID=8YFLogxK
U2 - 10.1111/j.1742-4658.2010.07819.x
DO - 10.1111/j.1742-4658.2010.07819.x
M3 - Article
C2 - 20849415
AN - SCOPUS:77957282695
VL - 277
SP - 4308
EP - 4321
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 20
ER -