Mitofusin-2 is a novel direct target of p53.
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.
Wang
Weilin
W
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.
Cheng
Xiaofei
X
Lu
Jianju
J
Wei
Jianfeng
J
Fu
Guanghou
G
Zhu
Feng
F
Jia
Changku
C
Zhou
Lin
L
Xie
Haiyang
H
Zheng
Shusen
S
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D004317:Doxorubicin / Q000494:pharmacology; D020558:GTP Phosphohydrolases; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human