http://www.cnr.it/ontology/cnr/individuo/prodotto/ID50188
Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway. (Articolo in rivista)
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- Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway. (Articolo in rivista) (literal)
- Anno
- 2005-01-01T00:00:00+01:00 (literal)
- Alternative label
Pascale A, Amadio M, Scapagnini G, Lanni C, Racchi M, Provenzani A, Govoni S, Alkon DL, Quattrone A. (2005)
Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway.
in Proceedings of the National Academy of Sciences of the United States of America
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- Pascale A, Amadio M, Scapagnini G, Lanni C, Racchi M, Provenzani A, Govoni S, Alkon DL, Quattrone A. (literal)
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- ISI Web of Science (WOS) (literal)
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- Department of Experimental and Applied Pharmacology, University of Pavia, Via Taramelli 14, 27100 Pavia, Italy. alessia.pascale@unipv.it (literal)
- Titolo
- Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway. (literal)
- Abstract
- More than 1 in 20 human genes bear in the mRNA 3' UTR a specific motif called the adenine- and uridine-rich element (ARE), which posttranscriptionally determines its expression in response to cell environmental signals. ELAV (embryonic lethal abnormal vision) proteins are the only known ARE-binding factors that are able to stabilize the bound mRNAs, thereby positively controlling gene expression. Here, we show that in human neuroblastoma SH-SY5Y cells, neuron-specific ELAV (nELAV) proteins (HuB, HuC, and HuD) are up-regulated and redistributed by 15 min of treatment with the activators of PKC phorbol esters and bryostatin-1. PKC stimulation also induces nELAV proteins to colocalize with the translocated PKCalpha isozyme preferentially on the cytoskeleton, with a concomitant increase of nELAV threonine phosphorylation. The same treatment promotes stabilization of growth-associated protein 43 (GAP-43) mRNA, a well known nELAV target, and induces an early increase in GAP-43 protein concentration, again only in the cytoskeletal cell fraction. Genetic or pharmacological inactivation of PKCalpha abolishes nELAV protein cytoskeletal up-regulation, GAP-43 mRNA stabilization, and GAP-43 protein increase, demonstrating the primary role of this specific PKC isozyme in the cascade of nELAV recruitment. Finally, in vivo PKC activation is associated with an up-regulation of nELAV proteins in the hippocampal rat brain. These findings suggest a model for gene expression regulation by nELAV proteins through a PKCalpha-dependent pathway that is relevant for the cellular programs in which ARE-mediated control plays a pivotal role.
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