FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27 Kip1 in acute myeloid leukemia

• Published in: Haematologica (Roma) Vol. 102; no. 8; pp. 1378 - 1389
• Main Authors: Peschel, Ines, Podmirseg, Silvio R., Taschler, Martin, Duyster, Justus, Götze, Katharina S., Sill, Heinz, Nachbaur, David, Jäkel, Heidelinde, Hengst, Ludger
• Format: Journal Article
• Language: English
• Published: Italy 01.08.2017
• Subjects: Cell Cycle Checkpoints; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; fms-Like Tyrosine Kinase 3 - metabolism; Humans; Leukemia, Myeloid, Acute - metabolism; Phosphorylation; Protein Kinase Inhibitors - metabolism; Tandem Repeat Sequences; Tumor Cells, Cultured; Tyrosine - metabolism

P27 (p27) can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. We observed that FLT3 and FLT3-ITD can directly bind and selectively phosphorylate p27 on this residue. Inhibition of FLT3-ITD in cell line...