Title: The requirement of c-Jun N-terminal kinase 2 in regulation of hypoxia-inducing factor-1α mRNA stability.
Authors: Zhang, Dongyun; Li, Jingxia; Zhang, Min; Gao, Guangxun; Zuo, Zhenghong; Yu, Yonghui; Zhu, Linda; Gao, Jimin; Huang, Chuanshu
Published In J Biol Chem, (2012 Oct 05)
Abstract: The mRNA of hif-1α is considered as being constitutively and ubiquitously expressed, regardless of the level of oxygen tension. However many recent reports have showed that hif-1α mRNA could be regulated by natural antisense transcripts, potential microRNAs, and low O(2). In this study, it was found that a deficiency of JNK2 expression reduced HIF-1α protein induction in response to nickel treatment resulting from the impaired expression of hif-1α mRNA. Both the promoter luciferase assay and mRNA degradation assay clearly showed that depletion of JNK2 affected stability of hif-1α mRNA, rather than regulated its transcription. In addition, nucleolin, a classic histone chaperone, was demonstrated to physically bind to hif-1α mRNA and maintain its stability. Further investigation indicated that JNK2 regulated nucleolin expression and might in turn stabilize hif-1α mRNA. Collectively, we provided one more piece of evidence for the oncogenic role of JNK2 and nucleolin in regulating the cancer microenvironments by controlling HIF-1α expression.
PubMed ID: 22910906
MeSH Terms: Animals; Gene Expression Regulation/physiology*; HEK293 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis*; Hypoxia-Inducible Factor 1, alpha Subunit/genetics; Mice; Mice, Knockout; MicroRNAs/genetics; MicroRNAs/metabolism; Mitogen-Activated Protein Kinase 9/genetics; Mitogen-Activated Protein Kinase 9/metabolism*; NIH 3T3 Cells; Oncogene Proteins/genetics; Oncogene Proteins/metabolism; Phosphoproteins/biosynthesis*; RNA Stability/physiology*; RNA, Messenger/genetics; RNA, Messenger/metabolism*; RNA-Binding Proteins/biosynthesis*; Tumor Microenvironment/physiology