scholarly journals CK2 Regulation: Perspectives in 2021

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1361
Author(s):  
Scott E. Roffey ◽  
David W. Litchfield
Keyword(s):  
Protein Kinase Ck2 ◽  
Regulatory Mechanism ◽  
Biological Processes ◽  
Single Mechanism ◽  
Parkinson’S Diseases ◽  
Damage Response ◽  
Substrate Level ◽  
Kinase Ck2 ◽  
Selection Of ◽  
Constitutively Active

The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders including Alzheimer′s and Parkinson’s diseases, and COVID-19. Interestingly, no single mechanism describes how CK2 is regulated, including activation by external proteins or domains, phosphorylation, or dimerization. Furthermore, the kinase has an elongated activation loop that locks the kinase into an active conformation, leading CK2 to be labelled a constitutively active kinase. This presents an interesting paradox that remains unanswered: how can a constitutively active kinase regulate biological processes that require careful control? Here, we highlight a selection of studies where CK2 activity is regulated at the substrate level, and discuss them based on the regulatory mechanism. Overall, this review describes numerous biological processes where CK2 activity is regulated, highlighting how a constitutively active kinase can still control numerous cellular activities. It is also evident that more research is required to fully elucidate the mechanisms that regulate CK2 and what causes aberrant CK2 signaling in disease.

scholarly journals Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 338
Author(s):  
Mauro Rosales ◽  
Arielis Rodríguez-Ulloa ◽  
Vladimir Besada ◽  
Ailyn C. Ramón ◽  
George V. Pérez ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Protein Kinase Ck2 ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Attractive Therapeutic Target ◽  
Kinase Ck2 ◽  
The Impact ◽  
Ck2 Inhibitor ◽  
Target Effects

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

scholarly journals Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

2021 ◽  
Author(s):  
Mauro Rosales ◽  
Arielis Rodriguez-Ulloa ◽  
Vladimir Besada ◽  
Ailyn C. Ramon ◽  
George V. Perez ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Protein Kinase Ck2 ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Attractive Therapeutic Target ◽  
Kinase Ck2 ◽  
The Impact ◽  
Ck2 Inhibitor ◽  
Target Effects

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

Evidence for a single mechanism gating perceptual and long-term memory information into working memory

2020 ◽  
Author(s):  
Sam Verschooren ◽  
Yoav Kessler ◽  
Tobias Egner
Keyword(s):  
Working Memory ◽  
Long Term Memory ◽  
Sources Of Information ◽  
Term Memory ◽  
Source Selection ◽  
Single Mechanism ◽  
Gating Mechanism ◽  
Opening And Closing ◽  
Selection Of

An influential view of working memory (WM) holds that its’ contents are controlled by a selective gating mechanism that allows for relevant perceptual information to enter WM when opened, but shields WM contents from interference when closed. In support of this idea, prior studies using the reference-back paradigm have established behavioral costs for opening and closing the gate between perception and WM. WM also frequently requires input from long-term memory (LTM), but it is currently unknown whether a similar gate controls the selection of LTM representations into WM, and how WM gating of perceptual vs. LTM sources of information relate to each other. To address these key theoretical questions, we devised a novel version of the reference-back paradigm, where participants switched between gating perceptual and LTM information into WM. We observed clear evidence for gate opening and closing costs in both cases. Moreover, the pattern of costs associated with gating and source-switching indicated that perceptual and LTM information is gated into WM via a single gate, and rely on a shared source-selection mechanism. These findings extend current models of WM gating to encompass LTM information, and outline a new functional WM architecture.

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

scholarly journals Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically driven quantitative biomarkers

2021 ◽  
Author(s):  
Laure Fournier ◽  
Lena Costaridou ◽  
Luc Bidaut ◽  
Nicolas Michoux ◽  
Frederic E. Lecouvet ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Quantitative Imaging ◽  
A Priori ◽  
External Validation ◽  
Data Driven ◽  
Imaging Biomarkers ◽  
Clinical Validation ◽  
Biological Processes ◽  
Imaging Data ◽  
Selection Of

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

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