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

Genes Dev. 2018 Oct 1;32(19-20):1321-1331. doi: 10.1101/gad.315523.118. Epub 2018 Sep 18.


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.

Keywords: ERK; Nup153; Tpr; nuclear envelope; nuclear pore complex; nucleoporin; nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Interphase
  • Mice
  • Nuclear Envelope / metabolism
  • Nuclear Pore / physiology*
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Pore Complex Proteins / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*


  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • Proto-Oncogene Proteins
  • TPR protein, human
  • TPR protein, mouse
  • Extracellular Signal-Regulated MAP Kinases