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Review
. 2017 Jan:63:71-80.
doi: 10.1016/j.jbior.2016.09.003. Epub 2016 Sep 18.

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

Chandrika Gowda  1 , Chunhua Song  1 , Malika Kapadia  1 , Jonathon L Payne  2 , Tommy Hu  1 , Yali Ding  1 , Sinisa Dovat  3
Affiliations
Review

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

Chandrika Gowda et al. Adv Biol Regul. 2017 Jan.

Abstract

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.

Keywords: CX4945; Casein Kinase II (CK2); Ikaros; Leukemia; PP1; Phosphorylation; Protein phosphatase 1.

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Figures

Fig. 1
Fig. 1
Structure of Ikaros and CK2 phosphorylation sites.
Fig. 2
Fig. 2
Ikaros- CK2 axis in Leukemia and role of CK2 inhibitor (CX4945).
See this image and copyright information in PMC

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