Casein Kinase II-mediated Phosphorylation of NF-κB p65 Subunit Enhances Inducible Nitric-oxide Synthase Gene Transcription in Vivo

Chantôme, Aurélie; Pance, Alena; Gauthier, Nolwenn; Vandroux, David; Chenu, Julie; Solary, Éric; Jeannin, Jean–François; Reveneau, Sylvie

doi:10.1074/jbc.m313731200

Cited by 46 publications

(44 citation statements)

References 59 publications

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“…4 Cytoplasmic NF-AT (cytoplasmic nuclear factor of activated T cells (NF-Atc)) is phosphorylated by CKII and translocated into the nucleus. 5 RelA (p65) is phosphorylated at multiple serine residues such as Ser 529 , 6,7 Ser 536 , 8 and Ser 276 9 by CKII, IkB kinase (IKK), and protein kinase A (PKA)/mitogen and stress-activated protein kinase (MSK), respectively. PKA catalytic subunit binds with IkBa of NF-kB/IkB complex and remains inactive.…”

mentioning

confidence: 99%

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells

Manna

Sarkar

2006

Cell Death Differ

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The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P 3 -25) is known to possess antibacterial, anti-fungal, anti-tubercular, and local anesthetic activities. We studied the anti-tumorigenic activity of P 3 -25 and the role of nuclear transcription factor kappaB (NF-jB) in this process. In constitutive NF-jB-expressing cells, treatment with P 3 -25 inhibited the expression of NF-jB-dependent reporter gene, adhesion molecules, and cyclooxygenase. It downregulated phosphorylation of p65 by inhibiting upstream kinases, such as protein kinase A and casein kinase II, but did not alter NF-jB DNA-binding activity. Alone, P 3 -25 induced apoptosis in NF-jB-expressing and doxorubicin-resistant breast cancer cells, and in the presence of other chemotherapeutic agents, it potentiated apoptosis. Overall, our results suggest that P 3 -25 exerts antitumorigenic activity by inhibiting phosphorylation of p65, the transcriptionally active subunit of NF-jB by inhibiting its upstream kinases, and potentiates apoptosis mediated by chemotherapeutic agents. These results suggest novel approaches for designing of anticancer drugs for combination chemotherapy.

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confidence: 99%

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells

Manna

Sarkar

2006

Cell Death Differ

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“…Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that CK2a is a candidate (Table I). Consistently, it was previously shown that CK2a associates with the BCR moiety of BCR-Abl (24,25), and CK2 phosphorylates p65 (10)(11)(12). Therefore, we hypothesized that CK2a associated with not only BCR-Abl but also BCR and that CK2a is a critical kinase for BCR-mediated inflammation development in vivo and in vitro.…”

Section: Formation Of the Bcr-ck2a Complex Is Required For Inflammatisupporting

confidence: 52%

“…CK2 forms a heterocomplex composed of two catalytic a subunits and two regulatory subunits (9). It was reported that CK2 phosphorylates p65 (10)(11)(12), an action critical for NF-kB-mediated transcription (13,14), although a detailed molecular mechanism of how CK2 regulates the transcription has not been shown.…”

Section: B Reakpoint Cluster Region (Bcr) Protein Is a Unique Kinasementioning

confidence: 99%

Breakpoint Cluster Region–Mediated Inflammation Is Dependent on Casein Kinase II

Meng

Jiang

Atsumi

et al. 2016

The Journal of Immunology

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The breakpoint cluster region (BCR) is known as a kinase and cause of leukemia upon fusing to Abl kinase. In this study, we demonstrate that BCR associated with the α subunit of casein kinase II (CK2α), rather than BCR itself, is required for inflammation development. We found that BCR knockdown inhibited NF-κB activation in vitro and in vivo. Computer simulation, however, suggested that the putative BCR kinase domain has an unstable structure with minimal enzymatic activity. Liquid chromatography–tandem mass spectrometry analysis showed that CK2α associated with BCR. We found the BCR functions are mediated by CK2α. Indeed, CK2α associated with adaptor molecules of TNF-αR and phosphorylated BCR at Y177 to establish a p65 binding site after TNF-α stimulation. Notably, p65 S529 phosphorylation by CK2α creates a p300 binding site and increased p65-mediated transcription followed by inflammation development in vivo. These results suggest that BCR-mediated inflammation is dependent on CK2α, and the BCR–CK2α complex could be a novel therapeutic target for various inflammatory diseases.

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“…3A, lanes 11 and 12), a PKC inhibitor [33], and 5, 6 Dichlorobenzimidazole riboside (DRB; Fig. 3A, lanes 15 and 16), a CK II inhibitor [34], had no effect on the translocation of hS3 to the nucleus.…”

Section: Translocation Of Hs3 To the Nucleus Is Dependent Upon Erk1/2mentioning

confidence: 98%

Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress

2007

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Besides its role in translation and ribosome maturation, human ribosomal protein S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for abasic sites and 7, 8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro. Here, we demonstrate that hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated phosphorylation of a threonine residue (T42) of hS3. Two different ectopically expressed site-directed mutants of T42 failed to respond to conditions of genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its colocalization with 8-oxoG foci, raising the possibility that hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage.

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Casein Kinase II-mediated Phosphorylation of NF-κB p65 Subunit Enhances Inducible Nitric-oxide Synthase Gene Transcription in Vivo

Cited by 46 publications

References 59 publications

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells

Breakpoint Cluster Region–Mediated Inflammation Is Dependent on Casein Kinase II

Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress

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