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.
- 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].
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.