The Effects of Copper Modulation on CK2 Kinase Activity

2020 ◽  
Author(s):  
Fatimah Alfaran
Keyword(s):  
Kinase Activity ◽  
Ck2 Kinase

scholarly journals Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model.

2019 ◽  
Vol 5 (3) ◽  
pp. eaav5078 ◽  
Author(s):  
Ying Ao ◽  
Jie Zhang ◽  
Zuojun Liu ◽  
Minxian Qian ◽  
Yao Li ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Nuclear Lamina ◽  
Premature Aging ◽  
Lamin A ◽  
Catalytic Core ◽  
Prelamin A ◽  
Damage Repair ◽  
Nuclear Lamin ◽  
Activity Loss ◽  
Ck2 Kinase

Defective nuclear lamina protein lamin A is associated with premature aging. Casein kinase 2 (CK2) binds the nuclear lamina, and inhibiting CK2 activity induces cellular senescence in cancer cells. Thus, it is feasible that lamin A and CK2 may cooperate in the aging process. Nuclear CK2 localization relies on lamin A and the lamin A carboxyl terminus physically interacts with the CK2α catalytic core and inhibits its kinase activity. Loss of lamin A inLmna-knockout mouse embryonic fibroblasts (MEFs) confers increased CK2 activity. Conversely, prelamin A that accumulates inZmpste24-deficent MEFs exhibits a high CK2α binding affinity and concomitantly reduces CK2 kinase activity. Permidine treatment activates CK2 by releasing the interaction between lamin A and CK2, promoting DNA damage repair and ameliorating progeroid features. These data reveal a previously unidentified function for nuclear lamin A and highlight an essential role for CK2 in regulating senescence and aging.

scholarly journals CIGB-300 synthetic peptide, an antagonist of CK2 kinase activity, as a treatment for Covid-19. A computational biology approach

2021 ◽  
Author(s):  
Jamilet Miranda ◽  
Ricardo Bringas ◽  
Jorge Fernández de-Cossio ◽  
Yasser Perera
Keyword(s):  
Immune Response ◽  
Computational Biology ◽  
Rna Splicing ◽  
Kinase Activity ◽  
Viral Infections ◽  
Drug Repositioning ◽  
Early Stage ◽  
Host Interactions ◽  
First Choice ◽  
Ck2 Kinase

Drug repositioning became the first choice for treating Covid-19 patients due to the urgent need to deal with the pandemic. Similarities in the hijacking mechanisms used by SARS-CoV-2 and several type of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for the treatment of cancer. A recent study in cells infected with SARS-CoV-2 virus found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to CK2 phospho-acceptor sites. Recent preliminary results show an antiviral activity of CIGB-300 versus a surrogate model of coronavirus. Here we present a computational biology study that provides evidences at the molecular level of how CIGB-300 might interfere with SARS-CoV-2 life cycle inside infected human cells. First, from SARS-CoV studies, we infer the potential incidence of CIGB-300 in SARS-CoV-2 interference on immune response. Next, from the analysis of multiple Omics data, we propose the action of CIGB-300 since early stage of viral infections perturbing the virus hijacking of RNA splicing machinery. It was also predicted the interference of CIGB-300 in virus-host interactions responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Further, we provide evidences of CIGB-300 attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders.

scholarly journals Targeting CK2 mediated signaling to impair/tackle SARS-CoV-2 infection: a computational biology approach

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jamilet Miranda ◽  
Ricardo Bringas ◽  
Jorge Fernandez-de-Cossio ◽  
Yasser Perera-Negrin
Keyword(s):  
Immune Response ◽  
Antiviral Activity ◽  
Computational Biology ◽  
Rna Splicing ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Viral Infections ◽  
Antagonistic Effect ◽  
Functional Enrichment ◽  
Ck2 Kinase

Abstract Background Similarities in the hijacking mechanisms used by SARS-CoV-2 and several types of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for cancer treatment. A recent study in cells infected with SARS-CoV-2 found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to the CK2 phospho-acceptor sites. Recent preliminary results show the antiviral activity of CIGB-300 using a surrogate model of coronavirus. Here we present a computational biology study that provides evidence, at the molecular level, of how CIGB-300 may interfere with the SARS-CoV-2 life cycle within infected human cells. Methods Sequence analyses and data from phosphorylation studies were combined to predict infection-induced molecular mechanisms that can be interfered by CIGB-300. Next, we integrated data from multi-omics studies and data focusing on the antagonistic effect on the CK2 kinase activity of CIGB-300. A combination of network and functional enrichment analyses was used. Results Firstly, from the SARS-CoV studies, we inferred the potential incidence of CIGB-300 in SARS-CoV-2 interference on the immune response. Afterwards, from the analysis of multiple omics data, we proposed the action of CIGB-300 from the early stages of viral infections perturbing the virus hijacking of RNA splicing machinery. We also predicted the interference of CIGB-300 in virus-host interactions that are responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Furthermore, we provided evidence of how CIGB-300 may participate in the attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders. Conclusions Our computational analysis proposes putative molecular mechanisms that support the antiviral activity of CIGB-300.

Design, validation and efficacy of bisubstrate inhibitors specifically affecting ecto-CK2 kinase activity

2015 ◽  
Vol 471 (3) ◽  
pp. 415-430 ◽  
Author(s):  
Giorgio Cozza ◽  
Sofia Zanin ◽  
Stefania Sarno ◽  
Elena Costa ◽  
Cristina Girardi ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Design Validation ◽  
Bisubstrate Inhibitors ◽  
Ck2 Inhibitor ◽  
Ck2 Kinase

Starting from a purely ATP competitive CK2 inhibitor a much more potent and selective bi-substrate directed derivative has been designed. It is active on cellular ecto-CK2 and its multifunctional mode of binding has been determined by kinetic and mutational analyses.

scholarly journals CIGB-300 Synthetic Peptide, an Antagonist of CK2 Kinase Activity, as a Treatment for Covid-19. A Computational Biology Approach

2021 ◽  
Author(s):  
Jamilet Miranda ◽  
Ricardo Bringas ◽  
Jorge Fernandez-de-Cossio ◽  
Yasser Perera-Negrin
Keyword(s):  
Immune Response ◽  
Computational Biology ◽  
Kinase Activity ◽  
Early Stage ◽  
Enrichment Analysis ◽  
Antagonistic Effect ◽  
Functional Enrichment ◽  
Omics Data ◽  
Potential Benefits ◽  
Ck2 Kinase

Abstract Background: Similarities in the hijacking mechanisms used by SARS-CoV-2 and several type of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for the treatment of cancer. A recent study in cells infected with SARS-CoV-2 virus found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to CK2 phospho-acceptor sites. Recent preliminary results show an antiviral activity of CIGB-300 versus a surrogate model of coronavirus. Here we present a computational biology study that provides evidences at the molecular level of how CIGB-300 might interfere with SARS-CoV-2 life cycle inside infected human cells. Methods: Sequence analysis and phosphorylation studies data were combined to predict infection-induced molecular mechanism that can be interfered by CIGB-300. Next we integrated multi-omics data on SARS-CoV-2 infection and data on the antagonistic effect on CK2 kinase activity of CIGB-300 to predict the potential benefits of its treatment in COVID-19 patients. A combination of network and functional enrichment analysis was used.Results: First, from SARS-CoV studies, we infer the potential incidence of CIGB-300 in SARS-CoV-2 interference on immune response. Next, from the analysis of multiple Omics data, we propose the action of CIGB-300 since early stage of viral infections perturbing the virus hijacking of RNA splicing machinery. It was also predicted the interference of CIGB-300 in virus-host interactions responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Further, we provide evidences of CIGB-300 attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders.Conclusions: We have evidenced the potential benefits of using CIGB-300 to treat COVID-19 patients and strongly suggest its use since early stages of viral infection.

scholarly journals CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions

2013 ◽  
Vol 384 (1-2) ◽  
pp. 71-82 ◽  
Author(s):  
Sarah Lupp ◽  
Catalina Gumhold ◽  
Emmanuel Ampofo ◽  
Mathias Montenarh ◽  
Karen Rother
Keyword(s):  
Kinase Activity ◽  
Promoter Regions ◽  
Gene Expressions ◽  
Ck2 Kinase
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