Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B-Cdk1 activation.
The Int-6 protein has been originally identified as the product of a mouse gene being a frequent integration site of the mouse mammary tumour virus. Here, we show that reducing Int-6 expression by RNA interference in HeLa cells markedly alters mitosis progression. Defects in spindle formation, chromosome segregation and cytokinesis were observed. These abnormalities of mitosis completion are correlated with an inhibition of cyclin B-Cdk1 kinase activity, due to a prolonged inhibitory phosphorylated state of Cdk1. In line with this observation, the Wee1 tyrosine kinase that negatively controls Cdk1 was less efficiently inactivated during G2 in Int-6-depleted cells. These findings support the notion that the oncogenic properties associated with alteration of Int-6 originate from chromosomal instability.
Morris
Christelle
C
Laboratoire de Biologie Moléculaire de la Cellule, UMR5161-CNRS, IFR 128 Biosciences Lyon-Gerland, ENS de Lyon, 46, Allée d'Italie, 69364 Lyon, France.
Jalinot
Pierre
P
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D019926:Cyclin B / Q000037:antagonists & inhibitors*; D048749:Cytokinesis / Q000235:genetics; D039621:Eukaryotic Initiation Factor-3 / Q000032:analysis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000276:immunology / Q000378:metabolism
D018797:Cell Cycle Proteins; D019926:Cyclin B; D039621:Eukaryotic Initiation Factor-3; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase