Recombinant Human Forkhead box protein M1 (FOxM1), partial

Function

Required for the activation of Rho-associated protein kinases ROCK1 and ROCK2 and promotes epithelial-mesenchymal transition (PubMed:27399334). Enhances the activation of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) by binding simultaneously to the catalytic and regulatory subunits (PubMed:32606397). This relieves the inhibitory effect of the regulatory subunit on the kinase activity of the catalytic subunit, resulting in downstream signaling events such as AKT activation, GSK3B inactivation, and increased levels of SNAI1 (PubMed:32606397). Promotes glycolysis by binding to the pyruvate kinase PKM homotetramer to form a heterooctamer, inhibiting PKM activity (PubMed:33314660). Promotes the IMP4-mediated nuclear translocation of both PKM and the NF-kappa-B complex which increases transcription of VEGFA, leading to increased angiogenesis (PubMed:33314660)

Subcellular Location

Cytoplasm

Tissue Specificity

Expressed in thymus, testis, small intestine, colon followed by ovary. Appears to be expressed only in adult organs containing proliferating/cycling cells or in response to growth factors. Also expressed in epithelial cell lines derived from tumors. Not expressed in resting cells. Isoform 2 is highly expressed in testis

Subunit

Interacts with Rho-associated protein kinases ROCK1 and ROCK2; the interaction promotes ROCK activation (PubMed:27399334). Interacts with phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunits PIK3CA/p110alpha, PIK3CB/p110beta and PIK3CD/p110delta (via the catalytic domain) as well as with non-catalytic regulatory subunit PIK3R1/p85a; binds to the catalytic and regulatory subunits simultaneously which relieves the inhibitory effect of the regulatory subunit on the kinase activity of the catalytic subunit (PubMed:32606397). Interacts with pyruvate kinase PKM isoform M2 (PKM2); binds to the PKM2 homotetramer to form a heterooctamer, consisting of the PKM2 homotetramer with 4 copies of FOXM1, which reduces PKM2 activity, leading to promotion of glycolysis (PubMed:33314660). Interacts with the NFKB1/p50 and RELA/p65 subunits of the NF-kappa-B transcription factor complex; this promotes their nuclear translocation along with PKM2, leading to increased VEGFA transcription and angiogenesis (PubMed:33314660). Interacts with VPS11; the interaction promotes exosome-mediated release of VEGFA (PubMed:33314660)

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• Yao K.-M. et al. Molecular analysis of a novel winged helix protein, WIN. Expression pattern, DNA binding property, and alternative splicing within the DNA binding domain. — J. Biol. Chem. (1997)
• PubMed: CI-7CALJ9DN3DHUP (APR-)
• Zhang X. et al. A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. — Oncogene (2017)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Westendorf J.M. et al. Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope. — Proc. Natl. Acad. Sci. U.S.A. (1994)
• Tan Y. et al. Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes. — Mol. Cell. Biol. (2007)
• Fu Z. et al. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. — Nat. Cell Biol. (2008)