Mitofusin-2 is a novel direct target of p53

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2010.08.108· OSTI ID:22202790

Wang, Weilin; Cheng, Xiaofei; Lu, Jianju; Wei, Jianfeng ^[1]; Fu, Guanghou ^[2]; Zhu, Feng; Jia, Changku; Zhou, Lin; Xie, Haiyang ^[1]; Zheng, Shusen ^[1]

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1. Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, Key Lab of Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003 (China)
2. Department of Urology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

Research highlights: {yields} Mfn2 is a novel target gene of p53. {yields} Mfn2 mRNA and protein levels can be up-regulated in a p53-dependent manner. {yields} Mfn2 promoter activity can be elevated by the p53 protein. {yields} P53 protein binds the Mfn2 promoter directly both in vitro and in vivo. -- Abstract: The tumor suppressor p53 modulates transcription of a number of target genes involved in cell cycle arrest, apoptosis, DNA repair, and other important cellular responses. Mitofusin-2 (Mfn2) is a novel suppressor of cell proliferation that may also exert apoptotic effects via the mitochondrial apoptotic pathway. Through bioinformatics analysis, we identified a p53 binding site in the Mfn2 promoter. Consistent with this, we showed that the p53 protein binds the Mfn2 promoter directly both in vitro and in vivo. Additionally, we found that Mfn2 mRNA and protein levels are up-regulated in a p53-dependent manner. Furthermore, luciferase assays revealed that the activity of the wild-type Mfn2 promoter, but not a mutated version of the promoter, was up-regulated by p53. These results indicate that Mfn2 is a novel p53-inducible target gene, which provides insight into the regulation of Mfn2 and its associated activities in the inhibition of cell proliferation, promotion of apoptosis, and modulation of tumor suppression.

• OSTI ID: 22202790
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 400, Issue 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
DNA REPAIR
GENES
IN VITRO
IN VIVO
INHIBITION
LUCIFERASE
MESSENGER-RNA
MITOCHONDRIA
NEOPLASMS
PROMOTERS
TRANSCRIPTION