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Translational regulation of the expression of the ubiquitin E3 ligase Nedd4-1 by mTORC1-dependent signaling.

ABSTRACT: We found recently that mTORC1 regulates the biosynthesis of the ubiquitin E3 ligase Nedd4-1, but not the close homolog Nedd4-2. This regulatory process plays a key role in promoting neurite growth in neurons of the mammalian central nervous system. The molecular mechanism underlying this rather specific regulation likely involves a pyrimidine-rich sequence stretch near the putative transcriptional start site within the 5' untranslated region of the Nedd4-1 mRNA, which may play a crucial role in directing the assembly of the protein translation machinery. We postulate that the Nedd4-1 mRNA is a major target of the local translation machinery within neurons that can be translated in a spatially and temporally controlled manner in response to various stimuli. Based on this model, neuronal Nedd4-1 may not only be involved in the regulation of neurite growth but also in axon guidance, spine formation, and synaptic plasticity.

SUBMITTER: Hsia HE

PROVIDER: S-EPMC4594434 | biostudies-literature | 2015 Jul-Aug

REPOSITORIES: biostudies-literature

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Translational regulation of the expression of the ubiquitin E3 ligase Nedd4-1 by mTORC1-dependent signaling.

Hsia Hung-En HE Kawabe Hiroshi H

Communicative & integrative biology 20150701 4

We found recently that mTORC1 regulates the biosynthesis of the ubiquitin E3 ligase Nedd4-1, but not the close homolog Nedd4-2. This regulatory process plays a key role in promoting neurite growth in neurons of the mammalian central nervous system. The molecular mechanism underlying this rather specific regulation likely involves a pyrimidine-rich sequence stretch near the putative transcriptional start site within the 5' untranslated region of the Nedd4-1 mRNA, which may play a crucial role in ...[more]

PMID: 26479408

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