Nucleoporin levels regulate cell cycle progression and phase-specific gene expression.
The Nup107-160 complex, the largest subunit of the nuclear pore, is multifunctional. It mediates mRNA export in interphase, and has roles in kinetochore function, spindle assembly, and postmitotic nuclear pore assembly. We report here that the levels of constituents of the Nup107-160 complex are coordinately cell cycle-regulated. At mitosis, however, a member of the complex, Nup96, is preferentially downregulated. This occurs via the ubiquitin-proteasome pathway. When the levels of Nup96 are kept high, a significant delay in G1/S progression occurs. Conversely, in cells of Nup96(+/-) mice, which express low levels of Nup96, cell cycle progression is accelerated. These lowered levels of Nup96 yield specific defects in nuclear export of certain mRNAs and protein expression, among which are key cell cycle regulators. Thus, Nup96 levels regulate differential gene expression in a phase-specific manner, setting the stage for proper cell cycle progression.
Chakraborty
Papia
P
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Wang
Yaming
Y
Wei
Jen-Hsuan
JH
van Deursen
Jan
J
Yu
Hongtao
H
Malureanu
Liviu
L
Dasso
Mary
M
Forbes
Douglass J
DJ
Levy
David E
DE
Seemann
Joachim
J
Fontoura
Beatriz M A
BM
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; C119239:nuclear pore complex protein 96