Regulation of cellular proliferation in acute lymphoblastic leukemia by Casein Kinase II (CK2) and Ikaros

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• 作者：Chandrika Gowda^a ; Chunhua Song^a ; Malika Kapadia^a ; Jonathon L. Payne^a ; ^b ; Tommy Hu^a ; Yali Ding^a ; Sinisa Dovat^a ; ^{sdovat@hmc.psu.edu}
• 关键词：Ikaros ; Casein Kinase II (CK2) ; Leukemia ; CX4945 ; PP1 ; Protein phosphatase 1 ; Phosphorylation
• 刊名：Advances in Biological Regulation
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：63
• 期：Complete
• 页码：71-80
• 全文大小：449 K
• 卷排序：63

文摘

The IKZF1 gene encodes the Ikaros protein, a zinc finger transcriptional factor that acts as a master regulator of hematopoiesis and a tumor suppressor in leukemia. Impaired activity of Ikaros is associated with the development of high-risk acute lymphoblastic leukemia (ALL) with a poor prognosis. The molecular mechanisms that regulate Ikaros' function as a tumor suppressor and regulator of cellular proliferation are not well understood. We demonstrated that Ikaros is a substrate for Casein Kinase II (CK2), an oncogenic kinase that is overexpressed in ALL. Phosphorylation of Ikaros by CK2 impairs Ikaros' DNA-binding ability, as well as Ikaros' ability to regulate gene expression and function as a tumor suppressor in leukemia. Targeting CK2 with specific inhibitors restores Ikaros’ function as a transcriptional regulator and tumor suppressor resulting in a therapeutic, anti-leukemia effect in a preclinical model of ALL. Here, we review the genes and pathways that are regulated by Ikaros and the molecular mechanisms through which Ikaros and CK2 regulate cellular proliferation in leukemia.