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Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia
Open AccessArticle

Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia

1
School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
2
College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA
3
Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1718; https://doi.org/10.3390/ijms21051718
Received: 25 January 2020 / Revised: 20 February 2020 / Accepted: 29 February 2020 / Published: 3 March 2020
(This article belongs to the Special Issue Molecular Research on Acute Lymphoblastic Leukemia)
Ikaros is a DNA-binding protein that regulates gene expression and functions as a tumor suppressor in B-cell acute lymphoblastic leukemia (B-ALL). The full cohort of Ikaros target genes have yet to be identified. Here, we demonstrate that Ikaros directly regulates expression of the small GTPase, Rab20. Using ChIP-seq and qChIP we assessed Ikaros binding and the epigenetic signature at the RAB20 promoter. Expression of Ikaros, CK2, and RAB20 was determined by qRT-PCR. Overexpression of Ikaros was achieved by retroviral transduction, whereas shRNA was used to knockdown Ikaros and CK2. Regulation of transcription from the RAB20 promoter was analyzed by luciferase reporter assay. The results showed that Ikaros binds the RAB20 promoter in B-ALL. Gain-of-function and loss-of-function experiments demonstrated that Ikaros represses RAB20 transcription via chromatin remodeling. Phosphorylation by CK2 kinase reduces Ikaros’ affinity toward the RAB20 promoter and abolishes its ability to repress RAB20 transcription. Dephosphorylation by PP1 phosphatase enhances both Ikaros’ DNA-binding affinity toward the RAB20 promoter and RAB20 repression. In conclusion, the results demonstrated opposing effects of CK2 and PP1 on expression of Rab20 via control of Ikaros’ activity as a transcriptional regulator. A novel regulatory signaling network in B-cell leukemia that involves CK2, PP1, Ikaros, and Rab20 is identified. View Full-Text
Keywords: Ikaros; CK2; PP1; RAB20; B-ALL Ikaros; CK2; PP1; RAB20; B-ALL
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MDPI and ACS Style

Payne, J.L; Song, C.; Ding, Y.; Dhanyamraju, P.K.; Bamme, Y.; Schramm, J.W; Desai, D.; Sharma, A.; Gowda, C.; Dovat, S. Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci. 2020, 21, 1718. https://doi.org/10.3390/ijms21051718

AMA Style

Payne JL, Song C, Ding Y, Dhanyamraju PK, Bamme Y, Schramm JW, Desai D, Sharma A, Gowda C, Dovat S. Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences. 2020; 21(5):1718. https://doi.org/10.3390/ijms21051718

Chicago/Turabian Style

Payne, Jonathon L; Song, Chunhua; Ding, Yali; Dhanyamraju, Pavan K.; Bamme, Yevgeniya; Schramm, Joseph W; Desai, Dhimant; Sharma, Arati; Gowda, Chandrika; Dovat, Sinisa. 2020. "Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia" Int. J. Mol. Sci. 21, no. 5: 1718. https://doi.org/10.3390/ijms21051718

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