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Tpr regulates the total number of nuclear pore complexes per cell nucleus

The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear...

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Detalles Bibliográficos
Autores principales: McCloskey, Asako, Ibarra, Arkaitz, Hetzer, Martin W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169833/
https://www.ncbi.nlm.nih.gov/pubmed/30228202
http://dx.doi.org/10.1101/gad.315523.118
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author McCloskey, Asako
Ibarra, Arkaitz
Hetzer, Martin W.
author_facet McCloskey, Asako
Ibarra, Arkaitz
Hetzer, Martin W.
author_sort McCloskey, Asako
collection PubMed
description The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear envelope remain unclear. Here, we report that depletion of the NPC basket protein Tpr, but not Nup153, dramatically increases the total NPC number in various cell types. This negative regulation of Tpr occurs via a phosphorylation cascade of extracellular signal-regulated kinase (ERK), the central kinase of the mitogen-activated protein kinase (MAPK) pathway. Tpr serves as a scaffold for ERK to phosphorylate the nucleoporin (Nup) Nup153, which is critical for early stages of NPC biogenesis. Our results reveal a critical role of the Nup Tpr in coordinating signal transduction pathways during cell proliferation and the dynamic organization of the nucleus.
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spelling pubmed-61698332018-10-12 Tpr regulates the total number of nuclear pore complexes per cell nucleus McCloskey, Asako Ibarra, Arkaitz Hetzer, Martin W. Genes Dev Research Paper The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear envelope remain unclear. Here, we report that depletion of the NPC basket protein Tpr, but not Nup153, dramatically increases the total NPC number in various cell types. This negative regulation of Tpr occurs via a phosphorylation cascade of extracellular signal-regulated kinase (ERK), the central kinase of the mitogen-activated protein kinase (MAPK) pathway. Tpr serves as a scaffold for ERK to phosphorylate the nucleoporin (Nup) Nup153, which is critical for early stages of NPC biogenesis. Our results reveal a critical role of the Nup Tpr in coordinating signal transduction pathways during cell proliferation and the dynamic organization of the nucleus. Cold Spring Harbor Laboratory Press 2018-10-01 /pmc/articles/PMC6169833/ /pubmed/30228202 http://dx.doi.org/10.1101/gad.315523.118 Text en © 2018 McCloskey et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
McCloskey, Asako
Ibarra, Arkaitz
Hetzer, Martin W.
Tpr regulates the total number of nuclear pore complexes per cell nucleus
title Tpr regulates the total number of nuclear pore complexes per cell nucleus
title_full Tpr regulates the total number of nuclear pore complexes per cell nucleus
title_fullStr Tpr regulates the total number of nuclear pore complexes per cell nucleus
title_full_unstemmed Tpr regulates the total number of nuclear pore complexes per cell nucleus
title_short Tpr regulates the total number of nuclear pore complexes per cell nucleus
title_sort tpr regulates the total number of nuclear pore complexes per cell nucleus
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169833/
https://www.ncbi.nlm.nih.gov/pubmed/30228202
http://dx.doi.org/10.1101/gad.315523.118
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