Signalling pathways regulating nucleo-cytoplasmic shuttling of the mRNA-binding protein HuR.
During the last decade evidence from numerous studies has been accumulated demonstrating that posttranscriptional gene regulation including mRNA turnover and translation is an important paradigm of eukaryotic gene expression contributing to the vast majority of cellular processes including cell growth and differentiation, metabolism, migration, and cellular senescence. Accordingly, a large number of reports have documented that the Human antigen R (HuR), a ubiquitously expressed member of the ELAV protein family, is one of the major actors in this scenario. Consequently, HuR is implicated in a large variety of pathologies in which deregulated stabilisation of many short-lived key mRNAs is causally linked with the onset and course of disease. Since HuR is most abundantly localised within the cell nucleus, export of HuR to the cytoplasm seems a major prerequisite for its stabilising effects on its cognate target adenylate- and uridylate-rich elements (AREs) containing cargo mRNAs. Although, the list of reports demonstrating a critical involvement of different signalling cascades in HuR-triggered mRNA functions is steadily growing, the mechanisms underlying HuR trafficking are not well understood. For this reason, the review will cover the most recent advances of knowledge of signalling cascades involved in the stimulus-dependent nucleo-cytoplasmic HuR shuttling and a special emphasis will be put on the possible regulatory role of posttranslational HuR modification.
Doller
Anke
A
Pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Pfeilschifter
Josef
J
Eberhardt
Wolfgang
W
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D003593:Cytoplasm / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008745:Methylation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction; D000099190:MAP-Kinase-Activated Kinase 2
D055372:AMP-Activated Protein Kinases; D000954:Antigens, Surface; D064447:Checkpoint Kinase 2; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000099190:MAP-Kinase-Activated Kinase 2; C098770:ELAVL1 protein, human; C578634:CHEK2 protein, human