scholarly journals Epigenetic regulation of gene expression by Ikaros, HDAC1 and Casein Kinase II in leukemia

Leukemia ◽  
2015 ◽  
Vol 30 (6) ◽  
pp. 1436-1440 ◽  
Author(s):  
C Song ◽  
X Pan ◽  
Z Ge ◽  
C Gowda ◽  
Y Ding ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Regulation Of Gene Expression ◽  
Casein Kinase Ii ◽  
Casein Kinase

scholarly journals Casein Kinase II Phosphorylates the Fragile X Mental Retardation Protein and Modulates Its Biological Properties

2002 ◽  
Vol 22 (24) ◽  
pp. 8438-8447 ◽  
Author(s):  
Mikiko C. Siomi ◽  
Kyoko Higashijima ◽  
Akira Ishizuka ◽  
Haruhiko Siomi
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Fragile X ◽  
Regulation Of Gene Expression ◽  
Phosphorylation Site ◽  
Casein Kinase Ii ◽  
Biological Properties ◽  
Casein Kinase

ABSTRACT Fragile X syndrome is caused by loss of FMR1 protein expression. FMR1 binds RNA and associates with polysomes in the cytoplasm; thus, it has been proposed to function as a regulator of gene expression at the posttranscriptional level. Posttranslational modification of FMR1 had previously been suggested to regulate its activity, but no experimental support for this model has been reported to date. Here we report that FMR1 in Drosophila melanogaster (dFMR1) is phosphorylated in vivo and that the homomer formation and the RNA-binding activities of dFMR1 are modulated by phosphorylation in vitro. Identification of a protein phosphorylating dFMR1 showed it to be Drosophila casein kinase II (dCKII). dCKII directly interacts with and phosphorylates dFMR1 in vitro. The phosphorylation site in dFMR1 was identified as Ser406, which is highly conserved among FMR1 family members from several species. Using mass spectrometry, we established that Ser406 of dFMR1 is indeed phosphorylated in vivo. Furthermore, human FMR1 (hFMR1) is also phosphorylated in vivo, and alteration of the conserved Ser500 in hFMR1 abolishes phosphorylation by CKII in vitro. These studies support the model that the biological functions of FMR1, such as regulation of gene expression, are likely regulated by its phosphorylation.

Protein signaling and regulation of gene transcription in leukemia: role of the Casein Kinase II-Ikaros axis

2016 ◽  
Vol 64 (3) ◽  
pp. 735-739 ◽  
Author(s):  
Chandrika S Gowda ◽  
Chunhua Song ◽  
Yali Ding ◽  
Malika Kapadia ◽  
Sinisa Dovat
Keyword(s):  
Gene Transcription ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Lymphoblastic Leukemia ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Casein Kinase Ii ◽  
Casein Kinase ◽  
Protein Signaling

Protein signaling and regulation of gene expression are the two major mechanisms that regulate cellular proliferation in leukemia. Discerning the function of these processes is essential for understanding the pathogenesis of leukemia and for developing the targeted therapies. Here, we provide an overview of one of the mechanisms that regulates gene transcription in leukemia. This mechanism involves the direct interaction between Casein Kinase II (CK2) and the Ikaros transcription factor. Ikaros (IKZF1) functions as a master regulator of hematopoiesis and a tumor suppressor in acute lymphoblastic leukemia (ALL). Impaired Ikaros function results in the development of high-risk leukemia. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. In vivo, Ikaros is a target for CK2, a pro-oncogenic kinase. CK2 directly phosphorylates Ikaros at multiple amino acids. Functional experiments showed that CK2-mediated phosphorylation of Ikaros, regulates Ikaros’ DNA binding affinity, subcellular localization and protein stability. Recent studies revealed that phosphorylation of Ikaros by CK2 regulates Ikaros binding and repression of the terminal deoxytransferase (TdT) gene in normal thymocytes and in T-cell ALL. Available data suggest that the oncogenic activity of CK2 in leukemia involves functional inactivation of Ikaros and provide a rationale for CK2 inhibitors as a potential treatment for ALL.

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