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.