Depletion of the nucleolar protein nucleostemin causes G1 cell cycle arrest via the p53 pathway.
Nucleostemin (NS) is a nucleolar protein expressed in adult and embryo-derived stem cells, transformed cell lines, and tumors. NS decreases when proliferating cells exit the cell cycle, but it is unknown how NS is controlled, and how it participates in cell growth regulation. Here, we show that NS is down-regulated by the tumor suppressor p14(ARF) and that NS knockdown elevates the level of tumor suppressor p53. NS knockdown led to G1 cell cycle arrest in p53-positive cells but not in cells in which p53 was genetically deficient or depleted by small interfering RNA knockdown. These results demonstrate that, in the cells investigated, the level of NS is regulated by p14(ARF) and the control of the G1/S transition by NS operates in a p53-dependent manner.
Ma
Hanhui
H
Program in Cell Dynamics, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pederson
Thoru
T
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002466:Cell Nucleolus / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D016193:G1 Phase; D019204:GTP-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000172:deficiency; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D002352:Carrier Proteins; C469949:GNL3 protein, human; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors