TY - JOUR
T1 - Signaling pathways and regulation of gene expression in hematopoietic cells
AU - Bogush, Daniel
AU - Schramm, Joseph
AU - Ding, Yali
AU - He, Bing
AU - Singh, Chingakham
AU - Sharma, Arati
AU - Tukaramrao, Diwakar Bastihalli
AU - Iyer, Soumya
AU - Desai, Dhimant
AU - Nalesnik, Gregory
AU - Hengst, Jeremy
AU - Bhalodia, Riya
AU - Gowda, Chandrika
AU - Dovat, Sinisa
N1 - Funding Information:
This work was supported by National Institutes of Health R01CA209829 (SD); R01CA213912 (SD); T32CA060395 (JS); Hyundai Hope on Wheels Scholar Grant (SD) and Young Investigator award (JS), Four Diamonds Fund of the Pennsylvania State University College of Medicine (to SD, CG and JS); Bear Necessities Pediatric Cancer Foundation , and the John Wawrzynowicz Leukemia Research Scholar Endowment (to SD).
Publisher Copyright:
© 2022
PY - 2023/5
Y1 - 2023/5
N2 - Cellular functions are regulated by signal transduction pathway networks consisting of protein-modifying enzymes that control the activity of many downstream proteins. Protein kinases and phosphatases regulate gene expression by reversible phosphorylation of transcriptional factors, which are their direct substrates. Casein kinase II (CK2) is a serine/threonine kinase that phosphorylates a large number of proteins that have critical roles in cellular proliferation, metabolism and survival. Altered function of CK2 has been associated with malignant transformation, immunological disorders and other types of diseases. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase, which regulates the phosphorylation status of many proteins that are essential for cellular functions. IKAROS is a DNA-binding protein, which functions as a regulator of gene transcription in hematopoietic cells. CK2 directly phosphorylates IKAROS at multiple phosphosites which determines IKAROS activity as a regulator of gene expression. PP1 binds to IKAROS via the PP1-consensus recognition site and dephosphorylates serine/threonine residues that are phosphorylated by CK2. Thus, the interplay between CK2 and PP1 signaling pathways have opposing effects on the phosphorylation status of their mutual substrate – IKAROS. This review summarizes the effects of CK2 and PP1 on IKAROS role in regulation of gene expression and its function as a tumor suppressor in leukemia.
AB - Cellular functions are regulated by signal transduction pathway networks consisting of protein-modifying enzymes that control the activity of many downstream proteins. Protein kinases and phosphatases regulate gene expression by reversible phosphorylation of transcriptional factors, which are their direct substrates. Casein kinase II (CK2) is a serine/threonine kinase that phosphorylates a large number of proteins that have critical roles in cellular proliferation, metabolism and survival. Altered function of CK2 has been associated with malignant transformation, immunological disorders and other types of diseases. Protein phosphatase 1 (PP1) is a serine/threonine phosphatase, which regulates the phosphorylation status of many proteins that are essential for cellular functions. IKAROS is a DNA-binding protein, which functions as a regulator of gene transcription in hematopoietic cells. CK2 directly phosphorylates IKAROS at multiple phosphosites which determines IKAROS activity as a regulator of gene expression. PP1 binds to IKAROS via the PP1-consensus recognition site and dephosphorylates serine/threonine residues that are phosphorylated by CK2. Thus, the interplay between CK2 and PP1 signaling pathways have opposing effects on the phosphorylation status of their mutual substrate – IKAROS. This review summarizes the effects of CK2 and PP1 on IKAROS role in regulation of gene expression and its function as a tumor suppressor in leukemia.
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U2 - 10.1016/j.jbior.2022.100942
DO - 10.1016/j.jbior.2022.100942
M3 - Review article
C2 - 36621151
AN - SCOPUS:85145852039
SN - 2212-4926
VL - 88
JO - Advances in Biological Regulation
JF - Advances in Biological Regulation
M1 - 100942
ER -