FOXO3-dependent CDKN1B gene expression

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R-HSA-9699575
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Reaction [omitted]
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Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
29309929 FoxO transcription factors in cancer metabolism

Yadav, RK, Chauhan, AS, Zhuang, L, Gan, B

Semin. Cancer Biol. 2018
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
18787071 Age-dependent FOXO regulation of p27Kip1 expression via a conserved binding motif in rat muscle precursor cells

Lees, SJ, Childs, TE, Booth, FW

Am. J. Physiol., Cell Physiol. 2008
10783894 AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1

Medema, RH, Kops, GJ, Bos, JL, Burgering, BM

Nature 2000
28522571 FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia

Peschel, I, Podmirseg, SR, Taschler, M, Duyster, J, Götze, KS, Sill, H, Nachbaur, D, Jäkel, H, Hengst, L

Haematologica 2017
14981546 FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins

Scheijen, B, Ngo, HT, Kang, H, Griffin, JD

Oncogene 2004
11094066 Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1)

Dijkers, PF, Medema, RH, Pals, C, Banerji, L, Thomas, NS, Lam, EW, Burgering, BM, Raaijmakers, JA, Lammers, JW, Koenderman, L, Coffer, PJ

Mol. Cell. Biol. 2000
16266983 Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation

Brandts, CH, Sargin, B, Rode, M, Biermann, C, Lindtner, B, Schwäble, J, Buerger, H, Müller-Tidow, C, Choudhary, C, McMahon, M, Berdel, WE, Serve, H

Cancer Res. 2005
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