TY - JOUR
T1 - Nucleoporin Levels Regulate Cell Cycle Progression and Phase-Specific Gene Expression
AU - Chakraborty, Papia
AU - Wang, Yaming
AU - Wei, Jen Hsuan
AU - van Deursen, Jan
AU - Yu, Hongtao
AU - Malureanu, Liviu
AU - Dasso, Mary
AU - Forbes, Douglass J.
AU - Levy, David E.
AU - Seemann, Joachim
AU - Fontoura, Beatriz M.A.
N1 - Funding Information:
We thank A. Levay, D.R. Nussenzveig, and K. Jeganathan for assistance. We thank R. Basavappa, Z. Nawaz, and M. Matunis for reagents. This work was supported by NIH R01AI28900 and U54AI5715801 to D.E.L., and R01 GM07159-01 to B.M.A.F.
PY - 2008/11/11
Y1 - 2008/11/11
N2 - 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.
AB - 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.
KW - CELLBIO
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=55349118188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55349118188&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2008.08.020
DO - 10.1016/j.devcel.2008.08.020
M3 - Article
C2 - 19000832
AN - SCOPUS:55349118188
SN - 1534-5807
VL - 15
SP - 657
EP - 667
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -