scholarly journals Regulation of p53-MDMX Interaction by Casein Kinase 1 Alpha

2005 ◽  
Vol 25 (15) ◽  
pp. 6509-6520 ◽  
Author(s):  
Lihong Chen ◽  
Changgong Li ◽  
Yu Pan ◽  
Jiandong Chen
Keyword(s):  
Dna Damage ◽  
Central Region ◽  
Small Interfering Rna ◽  
Binding Protein ◽  
Casein Kinase ◽  
Ionizing Irradiation ◽  
Mouse Development ◽  
Casein Kinase 1 ◽  
Casein Kinase 1 Alpha ◽  
Interfering Rna

ABSTRACT MDMX is a homolog of MDM2 that is critical for regulating p53 function during mouse development. MDMX degradation is regulated by MDM2-mediated ubiquitination. Whether there are other mechanisms of MDMX regulation is largely unknown. We found that MDMX binds to the casein kinase 1 alpha isoform (CK1α) and is phosphorylated by CK1α. Expression of CK1α stimulates the ability of MDMX to bind to p53 and inhibit p53 transcriptional function. Regulation of MDMX-p53 interaction requires CK1α binding to the central region of MDMX and phosphorylation of MDMX on serine 289. Inhibition of CK1α expression by isoform-specific small interfering RNA (siRNA) activates p53 and further enhances p53 activity after ionizing irradiation. CK1α siRNA also cooperates with DNA damage to induce apoptosis. These results suggest that CK1α is a functionally relevant MDMX-binding protein and plays an important role in regulating p53 activity in the absence or presence of stress.

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

2011 ◽  
Vol 22 (16) ◽  
pp. 2834-2847 ◽  
Author(s):  
Zheng Meng ◽  
Luisa Capalbo ◽  
David M. Glover ◽  
William G. Dunphy
Keyword(s):  
Small Interfering Rna ◽  
Casein Kinase ◽  
Replication Forks ◽  
Casein Kinase 1 ◽  
Multifaceted Approach ◽  
Mediator Protein ◽  
Critical Residues ◽  
Interfering Rna ◽  
Stalled Replication Forks

The mediator protein Claspin is critical for the activation of the checkpoint kinase Chk1 during checkpoint responses to stalled replication forks. This function involves the Chk1-activating domain (CKAD) of Claspin, which undergoes phosphorylation on multiple conserved sites. These phosphorylations promote binding of Chk1 to Claspin and ensuing activation of Chk1 by ATR. However, despite the importance of this regulatory process, the kinase responsible for these phosphorylations has remained unknown. By using a multifaceted approach, we have found that casein kinase 1 gamma 1 (CK1γ1) carries out this function. CK1γ1 phosphorylates the CKAD of Claspin efficiently in vitro, and depletion of CK1γ1 from human cells by small interfering RNA (siRNA) results in dramatically diminished phosphorylation of Claspin. Consequently, the siRNA-treated cells display impaired activation of Chk1 and resultant checkpoint defects. These results indicate that CK1γ1 is a novel component of checkpoint responses that controls the interaction of a key checkpoint effector kinase with its cognate mediator protein.

scholarly journals Correction: miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α)

RSC Advances ◽  
2019 ◽  
Vol 9 (56) ◽  
pp. 32781-32781
Author(s):  
Ye Cao ◽  
Jiajia Zheng ◽  
Chentao Lv
Keyword(s):  
Cell Viability ◽  
Casein Kinase ◽  
Dedifferentiated Liposarcoma ◽  
Casein Kinase 1 ◽  
Casein Kinase 1 Alpha

Correction for ‘miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α)’ by Ye Cao et al., RSC Adv., 2019, 9, 22755–22763.

scholarly journals Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Morvarid Siri ◽  
Hamid Behrouj ◽  
Sanaz Dastghaib ◽  
Mozhdeh Zamani ◽  
Wirginia Likus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chemotherapy Resistance ◽  
Casein Kinase ◽  
Autophagy Flux ◽  
Casein Kinase 1 ◽  
Colorectal Cancer Cells ◽  
High Level ◽  
Casein Kinase 1 Alpha ◽  
Hct116 Cells

AbstractAdjuvant chemotherapy with 5-fluorouracil (5-FU) does not improve survival of patients suffering from a form of colorectal cancer (CRC) characterized by high level of microsatellite instability (MSI-H). Given the importance of autophagy and multi-drug-resistant (MDR) proteins in chemotherapy resistance, as well as the role of casein kinase 1-alpha (CK1α) in the regulation of autophagy, we tested the combined effect of 5-FU and CK1α inhibitor (D4476) on HCT116 cells as a model of MSI-H colorectal cancer. To achieve this goal, the gene expression of Beclin1 and MDR genes, ABCG2 and ABCC3 were analyzed using quantitative real-time polymerase chain reaction. We used immunoblotting to measure autophagy flux (LC3, p62) and flow cytometry to detect apoptosis. Our findings showed that combination treatment with 5-FU and D4476 inhibited autophagy flux. Moreover, 5-FU and D4476 combination therapy induced G2, S and G1 phase arrests and it depleted mRNA of both cell proliferation-related genes and MDR-related genes (ABCG2, cyclin D1 and c-myc). Hence, our data indicates that targeting of CK1α may increase the sensitivity of HCT116 cells to 5-FU. To our knowledge, this is the first description of sensitization of CRC cells to 5-FU chemotherapy by CK1α inhibitor. Graphic abstract

scholarly journals qiRNA is a new type of small interfering RNA induced by DNA damage

Nature ◽  
2009 ◽  
Vol 459 (7244) ◽  
pp. 274-277 ◽  
Author(s):  
Heng-Chi Lee ◽  
Shwu-Shin Chang ◽  
Swati Choudhary ◽  
Antti P. Aalto ◽  
Mekhala Maiti ◽  
...  
Keyword(s):  
Dna Damage ◽  
Small Interfering Rna ◽  
New Type ◽  
Interfering Rna

scholarly journals Lack of Casein Kinase 1 Delta Promotes Genomic Instability - The Accumulation of DNA Damage and Down-Regulation of Checkpoint Kinase 1

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170903 ◽  
Author(s):  
Yoshimi Endo Greer ◽  
Bo Gao ◽  
Yingzi Yang ◽  
Andre Nussenzweig ◽  
Jeffrey S. Rubin
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Casein Kinase ◽  
Down Regulation ◽  
Casein Kinase 1 ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

Effect of casein kinase 1α inhibition on autophagy flux and the AKT/phospho-β-catenin (S552) axis in HCT116, a RAS-mutated colorectal cancer cell line

2021 ◽  
pp. 1-10
Author(s):  
Hamid Behrouj ◽  
Atefeh Seghatoleslam ◽  
Pooneh Mokarram ◽  
Saeid Ghavami
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell Line ◽  
Casein Kinase ◽  
Colorectal Cancer Cell Line ◽  
Autophagy Flux ◽  
Casein Kinase 1 ◽  
Induced Apoptosis ◽  
Casein Kinase 1 Alpha

The Wnt/β-catenin pathway, which interferes with cell proliferation, differentiation, and autophagy, is commonly dysregulated in colorectal cancer (CRC). Mutation of the RAS oncogene is the most prevalent genetic alteration in CRC and has been linked to activation of protein kinase B (AKT) signaling. Phosphorylation of β-catenin at Ser 552 by AKT contributes to β-catenin stability, transcriptional activity, and increase of cell proliferation. Casein kinase 1 alpha (CK1α) is an enzyme that simultaneously regulates Wnt/β-catenin and AKT. The link of the AKT and Wnt pathway to autophagy in RAS-mutated CRC cells has not well identified. Therefore, we investigated how pharmacological CK1α inhibition (D4476) is involved in regulation of autophagy, Wnt/β-catenin, and AKT pathways in RAS-mutated CRC cell lines. qRT-PCR and immunoblotting experiments revealed that phospho-AKT (S473) and phospho-β-catenin (S552) are constitutively increased in RAS-mutated CRC cell lines, in parallel with augmented CK1α expression. The results also showed that D4476 significantly reduced the AKT/phospho-β-catenin (S552) axis concomitantly with autophagy flux inhibition in RAS-mutated CRC cells. Furthermore, D4476 significantly induced apoptosis in RAS-mutated CRC cells. In conclusion, our results indicate that CK1α inhibition reduces autophagy flux and promotes apoptosis by interfering with the AKT/phospho-β-catenin (S552) axis in RAS-mutated CRC cells.

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