Changes in importin levels promote nuclear proteasomal degradation of cell cycle-related proteins during THP-1 monocyte-to-macrophage differentiation

Abstract

Importin family nucleocytoplasmic transport receptors share thousands of cargo proteins. To elucidate cell regulatory mechanisms via transport regulation, we analyzed the levels of transport receptors by western blotting and quantified the total cellular and nuclear proteins during monocyte-to-macrophage differentiation of THP-1 cells using mass spectrometry. Importin-α1 decreased and importin-α5 increased during the differentiation. Cell cycle-related proteins decreased in both whole cells and nuclei, and proteasome-related proteins increased in the nuclei but not in whole cells. During the differentiation with importin-α1 overexpression, the nuclear levels of some cell division-related proteins recovered, and with importin-α5 knockdown, proteasome assembly factors decreased in the nuclei. In this differentiation, transport receptors reduce unnecessary nuclear proteins by abating import and promoting nuclear proteasomal degradation. This study demonstrates the importance of global nuclear transport control in cell regulation.