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Regulation of Ikaros function by casein kinase 2 and protein phosphatase 1

Content Provider	PubMed Central
Author	Song, Chunhua Li, Zhanjun Erbe, Amy K. Savic, Aleksandar Sinisa, Dovat
Copyright Year	2011
Abstract	The Ikaros gene encodes a zinc finger, DNA-binding protein that regulates gene transcription and chromatin remodeling. Ikaros is a master regulator of hematopoiesis and an established tumor suppressor. Moderate alteration of Ikaros activity (e.g. haploinsufficiency) appears to be sufficient to promote malignant transformation in human hematopoietic cells. This raises questions about the mechanisms that normally regulate Ikaros function and the potential of these mechanisms to contribute to the development of leukemia. The focus of this review is the regulation of Ikaros function by phosphorylation/dephosphorylation. Site-specific phosphorylation of Ikaros by casein kinase 2 (CK2) controls Ikaros DNA-binding ability and subcellular localization. As a consequence, the ability of Ikaros to regulate cell cycle progression, chromatin remodeling, target gene expression, and thymocyte differentiation are controlled by CK2. In addition, hyperphosphorylation of Ikaros by CK2 leads to decreased Ikaros levels due to ubiquitin-mediated degradation. Dephosphorylation of Ikaros by protein phosphatase 1 (PP1) acts in opposition to CK2 to increase Ikaros stability and restore Ikaros DNA binding ability and pericentromeric localization. Thus, the CK2 and PP1 pathways act in concert to regulate Ikaros activity in hematopoiesis and as a tumor suppressor. This highlights the importance of these signal transduction pathways as potential mediators of leukemogenesis via their role in regulating the activities of Ikaros.
Related Links	http://dx.doi.org/10.4331/wjbc.v2.i6.126
Starting Page	126
File Format	PDF
ISSN	19498454
e-ISSN	19498454
Journal	World Journal of Biological Chemistry
Issue Number	6
Volume Number	2
Language	English
Publisher	Baishideng Publishing Group Co., Limited
Publisher Date	2011-01-01
Access Restriction	Open
Rights Holder	Baishideng Publishing Group Co., Limited
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article

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