title: Transcriptional regulation of importin-α1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells.
abstract: The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1promoter. Reduction in the levels of importin-α1by JunD increased cytoplasmic levels of HuR, although it failed to alter whole cell HuR levels. Increased levels of endogenous JunD by depleting cellular polyamines also inhibited importin-α1expression and increased cytoplasmic HuR levels, whereas JunD silencing rescued importin-α1expression and enhanced HuR nuclear translocation in polyamine-deficient cells. Moreover, importin-α1silencing protected IECs against apoptosis, which was prevented by HuR silencing. These results indicate that JunD regulates HuR subcellular distribution by downregulating importin-α1, thus contributing to the maintenance of gut epithelium homeostasis.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Chung
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Robinson
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; jywang@som.umaryland.edu.|Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland; and.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000235:genetics*; D028901:alpha Karyopherins / Q000235:genetics*
chemical_list: D000067780:ELAV-Like Protein 1; D011073:Polyamines; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D028901:alpha Karyopherins
keywords: apoptosis; intestinal epithelial cells; nuclear pore complex; subcellular trafficking