| Autor: |
Hayashi Y; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan.; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan., Fujimura A; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan., Kato K; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan., Udagawa R; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan., Hirota T; Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, 3-8-1 Ariake, Koto-ku, Tokyo 135-8550, Japan., Kimura K; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan.; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan. |
| Abstrakt: |
The nucleolus is a dynamic nuclear body that has been demonstrated to disassemble at the onset of mitosis; the relationship between cell cycle progression and nucleolar integrity, however, remains poorly understood. We studied the role of nucleolar proteins in mitosis by performing a global analysis using small interfering RNAs specific to nucleolar proteins; we focused on nucleolar protein 11 (NOL11), with currently unknown mitotic functions. Depletion of NOL11 delayed entry into the mitotic phase owing to increased inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1) and aberrant accumulation of Wee1, a kinase that phosphorylates and inhibits Cdk1. In addition to effects on overall mitotic phenotypes, NOL11 depletion reduced ribosomal RNA (rRNA) levels and caused nucleolar disruption during interphase. Notably, mitotic phenotypes found in NOL11-depleted cells were recapitulated when nucleolar disruption was induced by depletion of rRNA transcription factors or treatment with actinomycin D. Furthermore, delayed entry into the mitotic phase, caused by the depletion of pre-rRNA transcription factors, was attributable to nucleolar disruption rather than to G 2 /M checkpoint activation or reduced protein synthesis. Our findings therefore suggest that maintenance of nucleolar integrity during interphase is essential for proper cell cycle progression to mitosis via the regulation of Wee1 and Cdk1. |
