CK2 phosphorylates AP-2α and increases its transcriptional activity

Ren, Kai; Xian, Shuanglin; He, Fangli; Zhang, Wenfeng; Ding, Xiaofeng; Wu, Yanyang; Yang, Liping; Zhou, Jianlin; Gao, Xiang; Zhang, Jian

doi:10.5483/bmbrep.2011.44.7.490

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…CK2 plays an important role in HER2/neu cell signaling process. However, elevated CK2 activity play a role in aberrant activation of factors responsible for cell signaling and the activation of transcriptional activity of Adaptor-associated kinase (Luo et al, 2003) and it may represents a potential therapeutic target (Ren et al, 2011). Present study found a CK2 phosphorylation site in the C-terminal region.…”

Section: Calcium Binding Domainmentioning

confidence: 46%

Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.

et al. 2014

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The protein kinase c-erbB-2 belongs to the family of receptor tyrosine kinase and is involved in oncogenesis. The present study predicts different phosphorylation sites of HER2/c-erbB-2 which are important in preventing or developing cancer, especially breast cancer. Sequence homology showed highest homology (77%) with epidermal growth factor receptor kinase domain. According to PROSITE search result, active sites of c-erbB-2 are N-lobe (glycine rich phosphate binding loop). Catalytic loop with presumptive catalytically active of Asp108 is phosphorylated by tyrosine protein kinase. A-loop, activation loop, becomes phosphorylated and activates the substrate binding. The study strengthens our knowledge regarding HER2 signaling by the detection of uncharacterized signaling proteins, establishing phosphorylation of an activation loop and helps us to make assumptions about the role of such previously unidentified proteins. On the basis of importance of HER2 in breast cancer as well as in other diseases, this study provides fruitful information for designing new therapeutic strategies.

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Section: Calcium Binding Domainmentioning

confidence: 46%

Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.

et al. 2014

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“…The expression plasmids HA-p53, Myc-CCDC106, EGFP-CCDC106, Myc-CK2α and HA-CK2β have been described previously [9, 22]. Site-directed mutagenesis was performed by overlap extension PCR to generate three CCDC106 mutants (S130A, S147A and S130/147A, where Ser-130, Ser-147 and both Ser-130 and Ser-47 were substituted to Ala, respectively).…”

Section: Methodsmentioning

confidence: 99%

CK2-mediated CCDC106 phosphorylation is required for p53 degradation in cancer progression

Ning

Wang

Liu

et al. 2019

J Exp Clin Cancer Res

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BackgroundDysfunction of p53 is a key cause of cancer development, while CCDC106 can reduce p53 stability and is associated with lung cancer. However, the roles of CCDC106 in other cancer types and its upstream regulators have not been investigated.MethodsThe phosphorylation status was investigated by in vitro kinase assay and Western blotting using phosphorylation-specific antibodies. Co-immunoprecipitation assay and GST-pulldown were used to detect protein interaction. Cell viability, apoptosis, colony formation, wound-healing and invasion assays were measured for in vitro functional analyses. The in vivo effect of CCDC106 on tumor growth was investigated using a subcutaneous xenograft tumor mouse model.ResultsWe demonstrated that CCDC106 knockdown enhanced apoptosis by stabilizing p53 and suppressed cell viability, colony formation, migration and invasion in cervical cancer HeLa and breast cancer MCF7 cells with wild-type p53 (wtp53), whereas CCDC106 overexpression exerted the opposite effects in normal breast epithelial HBL100 and cervical cancer SiHa cells with wtp53. However, CCDC106 had no similar effects on p53-mutant cervical and breast cancer cells (C33A and MDA-MB-231). Further study showed that CK2 interacts with CCDC106 through its regulatory β subunit and then phosphorylates CCDC106 at Ser-130 and Ser-147. The phosphorylation of CCDC106 at Ser-130 and Ser-147 is required for its interaction with p53 and nuclear localization, respectively. Inhibiting CCDC106 phosphorylation by substituting both Ser-130 and Ser-147 with alanine or treating cells with the CK2 inhibitor CX-4945 abrogated CCDC106-induced p53 degradation and its oncogenic function in cells with wtp53. Wildtype CCDC106, but not Ser-130/− 147 mutant CCDC106, enhanced tumor growth and p53 degradation in a xenograft mouse model. Moreover, suppression of CCDC106 increased CX-4945 sensitivity of cancer cells with wtp53.ConclusionThis study revealed a CK2/CCDC106/p53 signaling axis in the progression of breast and cervical cancers, which may provide a new therapeutic target for cancer treatment.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1137-8) contains supplementary material, which is available to authorized users.

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“…Other types of SLiM-binding proteins produce more complex data, such as calmodulin, an EF-hand protein that recognises aliphatic helices with variable spacing between the key hydrophobic residues that dock into the binding sites (Yap et al 2000;Benz et al 2022) (Figure 1B). Finally, post-translational modification sites tend to have very short and low complexity motifs, like the S/TxxE motif recognised by casein kinase 2, a serine/threonine kinase complex that phosphorylates different targets and has an acidic residue 3 positions after the modification serine or threonine as its main specificity determinant (Ren et al 2011;Xavier et al 2012;Liu et al 2016;Zhou et al 2017) (Figure 1C). Analysing peptides containing such low complexity motifs is difficult regardless of the quality of the generated data.…”

Section: Introductionmentioning

confidence: 99%

“…2022) ( Figure 1B) . Finally, post-translational modification sites tend to have very short and low complexity motifs, like the S/TxxE motif recognised by casein kinase 2, a serine/threonine kinase complex that phosphorylates different targets and has an acidic residue 3 positions after the modification serine or threonine as its main specificity determinant (Ren et al . 2011; Xavier et al .…”

Section: Introductionmentioning

confidence: 99%

Benchmarking computational tools for de novo motif discovery

Simonetti,

Ivarsson,

Davey

2024

Preprint

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STRUCTURED ABSTRACTMotivationHigh-throughput experimental methods aimed at uncovering domain-peptide interactions have created numerous use cases for bioinformatic tools capable of detecting short linear motifs (SLiMs). Over the past twenty years, countless motif discovery tools have been introduced. However, the evaluation of these tools generally focus on a single tool and use artificially generated test-sets that fail to capture the authentic context of motifs within proteomic data. Consequently, these evaluations fall short in addressing real-world use cases.ResultsIn the current work, five motif discovery tools and seven general sequence alignment tools were benchmarked on their capacity to find SLiMs in datasets of peptides of varying complexity built from curated SLiM instances from the Eukaryotic Linear Motif database. We explored the effect of dataset size, peptide lengths, background noise levels and motif complexity on the motif discovery of these tools. The main metric used to compare all tools outputs was the percentage of correctly aligned SLiM containing peptides. Two motif discovery tools (DEME and SLiMFinder) and a sequence alignment tool (OPAL) outperformed the rest of the tools when benchmarked with this metric, averaging over 70% correctly aligned motif-containing peptides. The performance of the motif discovery tools and OPAL were not affected by the sizes of the test-sets, while increasing peptide length and noise levels lowered the performances of all tools. For N-/C-terminal motifs all tools performed well, while for those motifs that had low motif complexity only DEME and SLiMFinder returned correctly aligned motifs for ∼50% or more of the datasets.Availabilityhttps://doi.org/10.5281/zenodo.10467208.

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CK2 phosphorylates AP-2α and increases its transcriptional activity

Cited by 8 publications

References 33 publications

Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.

Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.

CK2-mediated CCDC106 phosphorylation is required for p53 degradation in cancer progression

Benchmarking computational tools for de novo motif discovery

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