Thrombopoietin-Induced Differentiation of a Human Megakaryoblastic Leukemia Cell Line, CMK, Involves Transcriptional Activation of p21WAF1/Cip1 by STAT5

• DOI: 10.1128/mcb.17.5.2933
• Publication Date: 2015-10-09T22:07:41Z
• Authors: Itaru Matsumura; Jun Ishikawa; Koichi Nakajima; Kenji Oritani; Yoshiaki Tomiyama; Jun-Ichiro Miyagawa; Takashi Kato; Hiroshi Miyazaki; Yuji Matsuzawa; Yuzuru Kanakura
• Keywords: Thrombopoiesis; STAT5; Ectopic expression; Thrombopoietin receptor; CDK inhibitor

Although thrombopoietin (TPO) is known to play a fundamental role in both megakaryopoiesis and thrombopoiesis, the molecular mechanism of TPO-induced megakaryocytic differentiation not known. In human megakaryoblastic leukemia cell line, CMK, that showed some degree after culture with TPO, cyclin-dependent kinase (Cdk) inhibitor p21WAF1/Cip1, but p27Kip1, p16INK4A, p15INK4B, or p18INK4C, was found be upregulated an immediately early response TPO. The expression p21 sustained over period 5 days by treatment TPO large polyploid cells developed small undifferentiated cells, indicating close correlation between ligand-induced induction CMK cells. To examine potential roles Cdk inhibitors differentiation, were transfected p21, p27, p16 gene, together marker β-galactosidase, cultured medium alone for days. ectopic p27 led Overexpression N-terminal domain (amino acids [aa] 1 75) sufficient induce whereas C-terminal (aa 76 164) had little no effect on morphological features. Furthermore, we although induced tyrosine phosphorylation STAT3 STAT5 only binding activities STAT-binding sites locate promoter region gene (p21-SIE sites), thereby leading transactivation p21. These results suggested induction, possibly mediated through activated STAT5, could important differentiation.