期刊
GENES & DEVELOPMENT
卷 32, 期 19-20, 页码 1321-1331出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.315523.118
关键词
nucleus; nuclear envelope; nuclear pore complex; nucleoporin; Tpr; Nup153; ERK
资金
- Mass Spectrometry Core of the Salk Institute
- National Institutes of Health (NIH)-National Cancer Institute Cancer Center [P30 014195]
- Helmsley Center for Genomic Medicine
- NIH [R01NS096786]
- Nomis Foundation
- Glenn Center for Aging Research
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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