AKT1 induces caspase-mediated cleavage of the CDK inhibitor p27Kip1 during cell cycle progression in leukemia cells transformed by FLT3-ITD

作者：Yang Xinping; Liu Suiyang; Kharbanda Surender; Stone Richard M^*

来源：Leukemia Research, 2012, 36(2): 205-211.

DOI：10.1016/j.leukres.2011.09.006

• FLT-ITD
• AKT1
• PI3K
• Caspase 3
• p27Kip1
• Cell cycle
• AML

p27Kip1 cleavage and caspase-3 regulate cell cycle in human myeloma cells and B cells, however regulation of p27Kip1 cleavage during the cell cycle is not known. In BaF3-FLT3-ITD cells, p27Kip1 undergoes C-terminal cleavage. Inhibition of the PI3K/AKT pathway is associated with decreased cleavage of p27Kip1 and G1 phase arrest. A caspase-3 inhibitor reduces p27Kip1 cleavage and inhibits cell proliferation. Knockdown shRNA against AKT1 reduces cleavage of p27Kip1, inhibits caspase-3 activation, and is associated with a delay in cell cycle progression. Taken together, these findings indicate that AKT1 induces caspase-mediated cleavage of p27Kip1, required for G1-S progression in FLT3-ITD cells.

• 出版日期2012-2