Regulation of the mRNA-binding protein HuR by posttranslational modification: spotlight on phosphorylation.
The ubiquitous mRNA-binding protein human antigen R (HuR) and its neuronal relatives (HuB, HuC, HuD) participate in the post-transcriptional regulation of many AU-rich element-bearing mRNAs. In addition to its originally described role in controlling mRNA decay, the binding of HuR to target mRNAs can affect many aspects of mRNA processing including splicing, polyadenylation, intracellular trafficking, translation and modulation of mRNA repression by miRNAs. In accordance to the growing list of signalling events which are involved in regulating these different HuR functions, recent data implicate that posttranslational modification, namely protein kinase-triggered phosphorylation of HuR plays a crucial role in connecting extracellular signal inputs to a specific post-transcriptional program by HuR. Notably, in addition to directly targeting HuR functions, posttranslational modifications of HuR have a major impact on the sequestration and binding to various HuR ligand proteins as has been demonstrated e.g. for the 14-3-3 chaperones. However, the detailed mechanisms of how a specific modification of HuR coordinates different aspects in HuR regulation are currently poorly understood. Due to the fact that most of the described HuR activities are closely related to its subcellular localization and the binding to cargo mRNA, this review will focus on these aspects of HuR functions and their control by posttranslational modification, particularly by HuR phosphorylations by different protein kinases.
pharmazentrum frankfurt/ ZAFES, Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt am Main, Germany. w.eberhardt@em.uni-frankfurt.de
Wolfgang
W
Eberhardt
Anke
A
Doller
Josef
J
Pfeilschifter
D000818:Animals; D051959:ELAV Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D051959:ELAV Proteins; D012333:RNA, Messenger