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| Description | The HuR protein consists of 326 aa (36 kDa). HuR has three highly conserved motifs belonging to the RNA recognition motif (RRM) superfamily and a hinge region between RRMs 2 and 3 named the HuR nucleocytoplasmic shuttling (HNS) domain. It has been shown that the HNS domain regulates the localization of HuR by mediating its association with adaptor proteins for nuclear export such as pp32/PHAP-I and APRIL and with import factors transportin-1, transportin-2, and importin. |
| Expression | Ubiquitously expressed |
| Localisation | Predominantly nuclear but shuttles between the nuclear and the cytoplasm. |
| Function | HuR belongs to the ELAV/Hu family (embryonic lethal abnormal vision phenotype in flies) of RNA-binding proteins (RBPs). Like other Hu/ELAVL RBPs, HuR contains 3 RRM through which it binds to specific mRNA and influences their post-transcriptional expression. HuR exhibits a high affinity for adenosine and uracil- (AU-) rich elements (ARE) leading to the stabilization and/or transport of its target host messages. In addition to its role as an mRNA stabilizer and transporter, HuR has been shown to mediate the translation of mRNAs and rarely to repress translation. Moreover, HuR plays a key role in the enhancement of caspase-dependent apoptosis induced by extreme stress conditions. In response to a lethal stress, HuR accumulates in the cytoplasm, where it undergoes caspase-mediated cleavage. This cleavage appears to be important for pp32/PHAP-I - mediated enhancement of the caspase-dependent apoptosis. HuR was shown to play others critical functions in cells responding to immune stimuli, nutrient availability, and exposure to damaging agents. Similarly, it has an important regulatory function in the progression of cells through the division cycle, the implementation of differentiation programs, the promotion of cell migration, cell invasion and a malignant phenotype, and the inhibition of replicative senescence. |
| Entity | Cancer |
| Oncogenesis | Breast , Lung , Colon and Ovary cancer. Expression of HuR is increased in all cancer tissues compared to the normal-tissue counterparts. It exists a consistent correlation between HuR expression levels and advancing stages of malignancy. |
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| Entity | Cachexia |
| Disease | Cachexia, characterized by the excessive loss of skeletal muscle, is frequently seen in patients with chronic diseases such as cancer. The bioactive gas nitric oxide has been identified as an important player in cancer-induced cachexia because NO is directly involved in the loss of MyoD mRNA (a key factor needed for the myogenic process, which is destabilized during cachexia) and muscle fiber. These events are mediated by the ability of HuR to associate and stabilizes the message encoding the inducible NO synthase enzyme. |
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| Entity | Hypertension |
| Disease | Chronic hypertension is associated with functional and morphological alterations of the vessel wall (ie, dysfunctional vascular endothelium and thickening of the smooth muscle layer). The pathomechanisms accounting for hypertension-induced vascular alterations are likely to be multifactorial. HuR is not only an important factor controlling vascular gene expression, but it is also subject to control by vasoactive factors that regulate cGMP and cAMP levels and downregulate its expression. |
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| Entity | Paraneoplastic neurological disease |
| Disease | Paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is the family of Hu antigens (Hel-N1, HuC, HuD and HuR). |
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| Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. |
| Fan XC, Steitz JA. |
| EMBO J. 1998 Jun 15; 17(12): 3448-3460. |
| PMID 9628880 |
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| Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease. |
| King PH, Redden D, Palmgren JS, Nabors LB, Lennon VA. |
| J Autoimmun. 1999 Dec; 13(4): 435-443. |
| PMID 10585760 |
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| HuR and mRNA stability. |
| Brennan CM, Steitz JA. |
| Cell Mol Life Sci. 2001 Feb; 58(2): 266-277. Review. |
| PMID 11289308 |
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| RNAi-mediated HuR depletion leads to the inhibition of muscle cell differentiation. |
| van der Giessen K, Di-Marco S, Clair E, Gallouzi IE. |
| J Biol Chem. 2003 Nov 21; 278(47): 47119-47128. |
| PMID 12944397 |
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| NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. |
| Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D, Marette A, Gallouzi IE. |
| Mol Cell Biol. 2005 Aug; 25(15): 6533-6545. |
| PMID 16024790 |
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| Human-antigen R (HuR) expression in hypertension: downregulation of the mRNA stabilizing protein HuR in genetic hypertension. |
| Kloss S, Rodenbach D, Bordel R, Mulsch A. |
| Hypertension. 2005 Jun; 45(6): 1200-1206. |
| PMID 15883232 |
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| HuR: post-transcriptional paths to malignancy. |
| Lopez de Silanes I, Lal A, Gorospe M. |
| RNA Biol. 2005 Jan; 2(1): 11-13. |
| PMID 17132932 |
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| The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner. |
| Dormoy-Raclet V, Menard I, Clair E, Kurban G, Mazroui R, Di Marco S, von Roretz C, Pause A, Gallouzi IE. |
| Mol Cell Biol. 2007 Aug; 27(15): 5365-5380. |
| PMID 17548472 |
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| Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. |
| Mazroui R, Di Marco S, Clair E, von Roretz C, Tenenbaum SA, Keene JD, Saleh M, Gallouzi IE. |
| J Cell Biol. 2008 Jan 14; 180(1): 113-127. |
| PMID 18180367 |
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