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

World Journal of Biological Chemistry 2011年第6期2卷 126-131页

作者： Amy K Erbe Aleksandar Savic Sinisa Dovat Department of Human Oncology University of Wisconsin-MadisonMadisonWI 53792United States Clinic of Hematology Clinical Center of VojvodinaFaculty of MedicineUniversity in Novi SadNovi Sad21000Serbia Department of Pediatrics Pennsylvania State UniversityCollege of MedicineHersheyPA 17033-0850United States

The Ikaros gene encodes a zinc finger,DNA-binding protein that regulates gene transcription and chromatin *** is a master regulator of hematopoiesis and an established tumor *** alteration of Ikaros activity (***) appears to be sufficient to promote malignant transformation in human hematopoietic *** raises questions about the mechanisms that normally regulate Ikaros function and the potential of these mechanisms to contribute to the development of *** focus of this review is the regulation of Ikaros function by phosphorylation/***-specific phosphorylation of Ikaros by casein kinase 2 (CK2) controls Ikaros DNA-binding ability and subcellular *** a consequence,the ability of Ikaros to regulate cell cycle progression,chromatin remodeling,target gene expression,and thymocyte differentiation are controlled by *** addition,hyperphosphorylation of Ikaros by CK2 leads to decreased Ikaros levels due to ubiquitinmediated *** of Ikaros by protein phosphatase 1 (PP1) acts in opposition to CK2 to increase Ikaros stability and restore Ikaros DNA binding ability and pericentromeric ***,the CK2 and PP1 pathways act in concert to regulate Ikaros activity in hematopoiesis and as a tumor *** highlights the importance of these signal transduction pathways as potential mediators of leukemogenesis via their role in regulating the activities of Ikaros.

关键词： Ikaros Leukemia Zinc finger Transcription factor Casein kinase 2 Protein phosphatase 1 Phosphorylation

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Ikaros in hematopoiesis and leukemia

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World Journal of Biological Chemistry 2011年第6期2卷 105-107页

作者： Sinisa Dovat Department of Pediatrics Pennsylvania State UniversityCollege of Medicine

Ikaros is a gene whose activity is essential for normal *** acts as a master regulator of lymphoid and myeloid development as well as a tumor *** cells,Ikaros regulates gene expression via chromatin *** the past 15 years tremendous advances have been made in understanding the role of Ikaros in hematopoiesis and *** this Topic Highlights series of reviews,several groups of international experts in this field summarize the experimental data that is shaping the emerging picture of Ikaros function at the biochemical and cellular *** articles provide detailed analyses of recent scientific advancements and present models that will serve as a basis for future studies aimed at developing a better understanding of normal hematopoiesis and hematological malignancies and at accelerating the application of this knowledge in clinical practice.

关键词： Ikaros Hematopoiesis leukemia Chromatin remodeling

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Ikaros isoforms:The saga continues

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World Journal of Biological Chemistry 2011年第6期2卷 140-145页

作者： Laura A Perez-Casellas Aleksandar Savic Sinisa Dovat Department of Pediatrics University of Wisconsin-MadisonMadisonWI 53792United States Clinic of Hematology Clinical Center of VojvodinaFaculty of MedicineUniversity in Novi SadNovi Sad 21000Serbia Department of Pediatrics Pennsylvania State UniversityCollege of MedicineH085Division of Pediatric Hematology/OncologyHersheyPA 17033-0850United States

Through alternate splicing,the Ikaros gene produces multiple *** is essential for normal hematopoiesis and possesses tumor suppressor *** isoforms interact to form dimers and potentially multimeric *** Ikaros complexes produced by the presence of different Ikaros isoforms are hypothesized to confer distinct *** dominantnegative Ikaros isoforms have been shown to inhibit the tumor suppressor activity of full-length ***,we describe how Ikaros activity is regulated by the coordinated expression of the largest Ikaros isoforms IK-1 and *** IK-1 is described as full-length Ikaros,IK-H is the longest Ikaros ***-H,which includes residues coded by exon 3B (60 bp that lie between exons 3 and 4),is abundant in human but not murine hematopoietic *** residues that lie within the 20 amino acids encoded by exon 3B give IK-H DNA-binding characteristics that are distinct from those of ***,IK-H can potentiate or inhibit the ability of IK-1 to bind ***-H binds to the regulatory regions of genes that are upregulated by Ikaros,but not genes that are repressed by *** IK-1 localizes to pericentromeric heterochromatin,IK-H can be found in both pericentromeric and non-pericentromeric ***-silencing activity of gamma satellite DNA has been shown to depend on the binding of IK-H,but not other Ikaros *** unique features of IK-H,its influence on Ikaros activity,and the lack of IK-H expression in mice suggest that Ikaros function in humans may be more complex and possibly distinct from that in mice.

关键词： Ikaros Chromatin,Pericentromeric Transcription IK-H Leukemia γ satellite

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