FoxM1 regulates growth factor-induced expression of kinase-interacting stathmin (KIS) to promote cell cycle progression.
The Forkhead box M1 (FoxM1) transcription factor is essential for cell cycle progression and mitosis. FoxM1 regulates expression of Skp2 and Cks1, subunits of the SCF ubiquitin ligase complex, which ubiquitinates p27(Kip1) and targets it for degradation. Kinase-interacting stathmin (KIS) is a growth factor-dependent nuclear kinase that regulates cell cycle progression by phosphorylating p27(Kip1) to promote its nuclear export. Here we present an additional mechanism of FoxM1-mediated regulation of p27(Kip1) and provide evidence that FoxM1 regulates growth factor-induced expression of KIS. In cells harboring FoxM1 deletion or expressing FoxM1-short interfering RNA, the expression of KIS is impaired, leading to an accumulation of p27(Kip1) in the nucleus. Furthermore, we show that KIS is a direct transcriptional target of FoxM1. Thus FoxM1 promotes cell cycle progression by down-regulating p27(Kip1) through multiple mechanisms.
Petrovic
Vladimir
V
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607.
Costa
Robert H
RH
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607.
Lau
Lester F
LF
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607.
Raychaudhuri
Pradip
P
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607.
Tyner
Angela L
AL
Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607. Electronic address: atyner@uic.edu.
D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C530658:UHMK1 protein, human; C530659:Uhmk1 protein, mouse