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

Adv Biol Regul. 2017 Jan:63:71-80. doi: 10.1016/j.jbior.2016.09.003.

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

Affiliations

1 Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
2 Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; Loma Linda University, Loma Linda, CA, USA.
3 Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. Electronic address: [email protected].

PMID: 27666503 DOI: 10.1016/j.jbior.2016.09.003

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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