The promoter of the CDKN1B gene, encoding CDK inhibitor p27Kip1, contains forkhead box elements that are required for induction of CDKN1B gene transcription by FOXO transcription factors FOXO1, FOXO3 (Dijkers et al, 2000, Lees et al, 2008) and FOXO4 (Medema et al, 2000). Direct binding of FOXO transcription factors to the CDKN1B gene promoter has not been demonstrated. CDKN1B expression is downregulated by FLT3- and FLT3-ITD signaling as a consequence of AKT-dependent FOXO3 phosphorylation and nuclear export. Downregulation of CDKN1B may contribute to cellular proliferation downstream of FLT3 signaling (Brandts et al, 2005; Scheijen et al, 2004; reviewed in Kazi and Ronnstrand, 2019; Yadav et al, 2018). Active FLT3 may also promote cell cycle progression by directly phopshorylating and inhibiting CDKN1B (Peschel et al, 2017).
Kazi, JU, Rönnstrand, L
Zhuang, L, Yadav, RK, Chauhan, AS, Gan, B
Lees, SJ, Childs, TE, Booth, FW
Burgering, BM, Bos, JL, Kops, GJ, Medema, RH
Jäkel, H, Duyster, J, Nachbaur, D, Götze, KS, Sill, H, Taschler, M, Hengst, L, Podmirseg, SR, Peschel, I
Griffin, JD, Scheijen, B, Kang, H, Ngo, HT
Raaijmakers, JA, Burgering, BM, Banerji, L, Koenderman, L, Thomas, NS, Lammers, JW, Pals, C, Dijkers, PF, Coffer, PJ, Lam, EW, Medema, RH
Berdel, WE, Serve, H, Rode, M, Brandts, CH, Sargin, B, Buerger, H, McMahon, M, Choudhary, C, Biermann, C, Lindtner, B, Müller-Tidow, C, Schwäble, J
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