The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Hong, Huixian; Benveniste, Etty N.

doi:10.3390/biomedicines9121932

Cited by 21 publications

(23 citation statements)

References 121 publications

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“…With over 500 known substrates and being estimated to be responsible for up to 10% of the human phosphoproteome [ 2 , 4 ], CK2 is of significant importance. Additionally, to having more than one-third of its substrates implicated in gene expression and protein synthesis [ 5 ], CK2 plays a critical role in development and differentiation [ 4 ], immunity [ 6 , 7 ], and DNA damage repair [ 8 ]. It also is essential for survival as CK2α and CK2β knockouts in mouse embryos are lethal [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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Cancer is a leading cause of death worldwide. Casein kinase 2 (CK2) is commonly dysregulated in cancer, impacting diverse molecular pathways. CK2 is a highly conserved serine/threonine kinase, constitutively active and ubiquitously expressed in eukaryotes. With over 500 known substrates and being estimated to be responsible for up to 10% of the human phosphoproteome, it is of significant importance. A broad spectrum of diverse types of cancer cells has been already shown to rely on disturbed CK2 levels for their survival. The hallmarks of cancer provide a rationale for understanding cancer’s common traits. They constitute the maintenance of proliferative signaling, evasion of growth suppressors, resisting cell death, enabling of replicative immortality, induction of angiogenesis, the activation of invasion and metastasis, as well as avoidance of immune destruction and dysregulation of cellular energetics. In this work, we have compiled evidence from the literature suggesting that CK2 modulates all hallmarks of cancer, thereby promoting oncogenesis and operating as a cancer driver by creating a cellular environment favorable to neoplasia.

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Section: Introductionmentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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“…Given that most cellular proteins harbor CK2 acidophilic phosphorylation sites, it is not surprising that CK2 plays a wide range of roles in normal and disease states; aspects of these functions are discussed subsequently with a primary focus on nuclear and mitochondrial roles for CK2 and the involvement of CK2 in prostate, breast, and head and neck cancers. Other significant aspects of CK2 in cancer biology, such as roles in DNA synthesis and damage repair, immunological aspects, and hematological malignancies are discussed in other recent CK2 reviews [ 54 – 56 ].…”

Section: Basic Aspects Of Ck2 Biochemistrymentioning

confidence: 99%

Protein kinase CK2 – diverse roles in cancer cell biology and therapeutic promise

et al. 2022

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The association of protein kinase CK2 (formerly casein kinase II or 2) with cell growth and proliferation in cells was apparent at early stages of its investigation. A cancer-specific role for CK2 remained unclear until it was determined that CK2 was also a potent suppressor of cell death (apoptosis); the latter characteristic differentiated its function in normal versus malignant cells because dysregulation of both cell growth and cell death is a universal feature of cancer cells. Over time, it became evident that CK2 exerts its influence on a diverse range of cell functions in normal as well as in transformed cells. As such, CK2 and its substrates are localized in various compartments of the cell. The dysregulation of CK2 is documented in a wide range of malignancies; notably, by increased CK2 protein and activity levels with relatively moderate change in its RNA abundance. High levels of CK2 are associated with poor prognosis in multiple cancer types, and CK2 is a target for active research and testing for cancer therapy. Aspects of CK2 cellular roles and targeting in cancer are discussed in the present review, with focus on nuclear and mitochondrial functions and prostate, breast and head and neck malignancies.

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“…In the brain, CK2α is more abundant than in other tissues, with a predominance of the α subunit over α’ ( Ceglia et al, 2011 ). CK2 is localized in different cellular compartments, is involved in diverse processes such signal transduction, replication, translation, and metabolism ( Roffey and Litchfield, 2021 ), as well as roles in angiogenesis ( Montenarh, 2014 ), development and differentiation ( Götz and Montenarh, 2017 ), and the immune system ( Hong and Benveniste, 2021 ). Moreover, it is upregulated in many cancers ( Ahmad et al, 2005 ; Ruzzene and Pinna, 2010 ; Rowse et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Comparing Two Neurodevelopmental Disorders Linked to CK2: Okur-Chung Neurodevelopmental Syndrome and Poirier-Bienvenu Neurodevelopmental Syndrome—Two Sides of the Same Coin?

Ballardin

Cruz-Gamero

Bienvenu

et al. 2022

Front. Mol. Biosci.

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In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by de novo missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.

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The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Cited by 21 publications

References 121 publications

CK2 and the Hallmarks of Cancer

CK2 and the Hallmarks of Cancer

Protein kinase CK2 – diverse roles in cancer cell biology and therapeutic promise

Comparing Two Neurodevelopmental Disorders Linked to CK2: Okur-Chung Neurodevelopmental Syndrome and Poirier-Bienvenu Neurodevelopmental Syndrome—Two Sides of the Same Coin?

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