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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
N-Myc downstream-regulated gene 2 is involved in p53-mediated apoptosis
1Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Biotechnology Center, Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, China.
Abstract:
The tumor suppressor, p53, is a transcription factor which can modulate the transcription of a number of target genes that are involved in cell-cycle arrest and apoptosis. However, the apoptotic pathway mediated by p53 is not fully understood. Here, we showed that N-Myc downstream-regulated gene 2 (NDRG2) is a new target gene that is regulated by p53. NDRG2 mRNA and protein levels can be upregulated in a p53-dependent manner. The first intron of the NDRG2 gene contains a site that binds p53 directly and mediates wild-type p53-dependent transactivation. In addition, silencing of NDRG2 attenuates p53-mediated apoptosis, whereas overexpression of NDRG2 suppresses tumor cell growth, regardless of the presence or absence of p53. Our results indicate that NDRG2 is a novel p53-inducible target that is involved in the p53-mediated apoptosis pathway.
Insights
The tumor suppressor p53 regulates N-Myc downstream-regulated gene 2 (NDRG2), a novel target involved in apoptosis. NDRG2 influences p53-mediated apoptosis and tumor cell growth.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- The tumor suppressor p53 is a transcription factor crucial for regulating genes involved in cell-cycle arrest and apoptosis.
- The precise mechanisms of p53-mediated apoptosis are not fully elucidated.
Purpose of the Study:
- To identify novel target genes regulated by p53.
- To investigate the role of N-Myc downstream-regulated gene 2 (NDRG2) in p53-mediated apoptosis.
Main Methods:
- Investigated NDRG2 gene regulation by p53 using mRNA and protein level analysis.
- Identified a p53 binding site within the first intron of the NDRG2 gene.
- Assessed the impact of NDRG2 silencing and overexpression on p53-mediated apoptosis and tumor cell growth.
Main Results:
- NDRG2 mRNA and protein levels are upregulated in a p53-dependent manner.
- A direct binding site for p53 was identified in the NDRG2 gene's first intron, mediating transactivation.
- Silencing NDRG2 reduced p53-induced apoptosis, while NDRG2 overexpression inhibited tumor cell growth irrespective of p53 status.
Conclusions:
- NDRG2 is a novel p53-inducible gene.
- NDRG2 plays a significant role in the p53-mediated apoptotic pathway.
- NDRG2 functions as a tumor suppressor, impacting cell growth independently of p53.
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