Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1

Meng, Zheng; Capalbo, Luisa; Glover, David M.; Dunphy, William G.

doi:10.1091/mbc.e11-01-0048

Cited by 38 publications

(37 citation statements)

References 44 publications

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“…It has been reported that CK1g1 plays an important role in activating the ATR/Chk1 pathway by phosphorylating Claspin, which was identified as a Chk1-activating protein (23). In this study, we found that CK1g1 can phosphorylate NF-kB subunit p65 at Ser 536 , which promotes its ubiquitin-mediated degredation by E3 ligases COMMD1 and CUL2.…”

Section: Discussionmentioning

confidence: 53%

Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation

Wang

Tong

et al. 2014

The Journal of Immunology

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The casein kinase 1 (CK1) plays an important role in various biological processes by phosphorylating its target proteins. In this study, we demonstrate that CK1γ1 inhibits RNA virus–mediated activation of retinoic acid–inducible gene I (RIG-I) signaling by affecting the stability of NF-κB subunit p65. First, we found that ectopic expression of CK1γ1 inhibits RIG-I pathway–mediated activation of IFN-β, whereas knockdown of CK1γ1 potentiates the activation of IFN-β and NF-κB induced by Sendai virus (SeV). We then revealed that CK1γ1 interacts with p65 and specifically enhances its phosphorylation at Ser536 induced by SeV. By using an in vitro kinase assay, we confirmed that CK1γ1 can phosphorylate p65 at Ser536. We also showed that the kinase dead mutants CK1γ1K73A and CK1γ1N169A did not inhibit SeV-induced activation of IFN-β and NF-κB, suggesting that the kinase activity of CK1γ1 is critical for its inhibitory effect on RIG-I signaling. Additionally, we found that CK1γ1 also has the similar effect on TLR signaling. Further analysis indicated that CK1γ1 phosphorylates p65 and consequently promotes its degradation by ubiquitin E3 ligases CUL2 and COMMD1. These results revealed a novel negative regulatory manner of CK1γ1 on innate immune signaling.

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Section: Discussionmentioning

confidence: 53%

Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation

Wang

Tong

et al. 2014

The Journal of Immunology

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“…15), and CDC7 (16,17). Phosphorylation of CLASPIN at its N-terminus by PLK1 can also contribute to switching off CHK1 once the damage is repaired, thus allowing cells to progress in the cell cycle (18,19).…”

Section: Introductionmentioning

confidence: 99%

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

et al. 2016

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Coordination of the multiple processes underlying DNA replication is key for maintaining genome stability and preventing tumorigenesis. CLASPIN, a critical player in replication fork stabilization and checkpoint responses, must be tightly regulated during the cell cycle to prevent the accumulation of DNA damage. In this study, we used a quantitative proteomics approach and identified USP9X as a novel CLASPIN-interacting protein. USP9X is a deubiquitinase involved in multiple signaling and survival pathways whose tumor suppressor or oncogenic activity is highly context dependent. We found that USP9X regulated the expression and stability of CLASPIN in an S-phase-specific manner. USP9X depletion profoundly impairs the progression of DNA replication forks, causing unscheduled termination events with a frequency similar to CLASPIN depletion, resulting in excessive endogenous DNA damage. Importantly, restoration of CLASPIN expression in USP9X-depleted cells partially suppressed the accumulation of DNA damage. Furthermore, USP9X depletion compromised CHK1 activation in response to hydroxyurea and UV, thus promoting hypersensitivity to drug-induced replication stress. Taken together, our results reveal a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. Cancer Res; 76(8); 2384-93. Ó2016 AACR.

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“…Although the ATR-Chk1 kinase cascade is clearly the backbone of the ATR signaling pathway, several other protein kinases, such as ATM (6,7), CDKs (cyclin-dependent kinases) (8)(9)(10), PLK1 (polo-like kinase) (11)(12)(13)(14), AKT (15,16), and casein kinases (17,18), have been implicated in tuning the strength and dynamics of ATR signaling in different contexts. The effects of these kinases on ATR signaling suggest that the ATR pathway is intertwined with other signaling pathways and cellular programs.…”

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confidence: 99%

Nek1 kinase associates with ATR–ATRIP and primes ATR for efficient DNA damage signaling

Liu

Ouyang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The master checkpoint kinase ATR (ATM and Rad3-related) and its partner ATRIP (ATR-interacting protein) exist as a complex and function together in the DNA damage response. Unexpectedly, we found that the stability of the ATR-ATRIP complex is regulated by an unknown kinase independently of DNA damage. In search for this regulator of ATR-ATRIP, we found that a single member of the NIMA (never in mitosis A)-related kinase family, Nek1, is critical for initiating the ATR response. Upon DNA damage, cells lacking Nek1 failed to efficiently phosphorylate multiple ATR substrates and support ATR autophosphorylation at threnine 1989, one of the earliest events during the ATR response. The ability of Nek1 to promote ATR activation relies on the kinase activity of Nek1 and its interaction with ATR-ATRIP. Importantly, even in undamaged cells, Nek1 is required for maintaining the levels of ATRIP, the association between ATR and ATRIP, and the basal kinase activity of ATR. Thus, as an ATR-associated kinase, Nek1, enhances the stability and activity of ATR-ATRIP before DNA damage, priming ATR-ATRIP for a robust DNA damage response.

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Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1

Cited by 38 publications

References 44 publications

Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation

Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

Nek1 kinase associates with ATR–ATRIP and primes ATR for efficient DNA damage signaling

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