In vitro and in silico studies on substrate recognition and acceptance of human PKMYT1, a Cdk1 inhibitory kinase

Rohe, Alexander; Erdmann, Frank; Bäßler, Claudia; Wichapong, Kanin; Sippl, Wolfgang; Schmidtkunz, Karin

doi:10.1016/j.bmcl.2011.11.064

Cited by 17 publications

(15 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ablation of WEE1 and PKMYT1 expression can cause mitotic collapse and apoptosis of cancer cells ( 38 , 52 ). A small molecule tyrosine kinase inhibitor, PD166285, has been shown to inhibit PKMYT1 at low nanomolar concentrations ( 53 ). The PKMYT1 promoter contains a potential E-box sequence near the transcription start site.…”

Section: Resultsmentioning

confidence: 99%

Identification and Pharmacological Inactivation of the MYCN Gene Network as a Therapeutic Strategy for Neuroblastic Tumor Cells

Chayka

D’Acunto

Middleton

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Neuroblastic tumors are often addicted to the MYCN protooncogene.Results: Using a genome wide shRNA screen, we have identified key MYCN synthetic lethal genes.Conclusion: Chemical inhibition of the newly identified MYCN synthetic lethal genes selectively kills MYCN-amplified cell lines.Significance: Decoding the MYCN gene network will help to develop drugs for the treatment of neuroblastic tumors with activated MYCN.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification and Pharmacological Inactivation of the MYCN Gene Network as a Therapeutic Strategy for Neuroblastic Tumor Cells

Chayka

D’Acunto

Middleton

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…For instance, the human Myt1 kinase (PKMYT1) acts as a negative regulator of G2/M transition by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins and was up-regulated at 8 h.p.i. [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiles of human foreskin fibroblast cells in response to orf virus

et al. 2017

View full text Add to dashboard Cite

Orf virus has been utilized as a safe and efficient viral vector against not only diverse infectious diseases, but also against tumors. However, the nature of the genes triggered by the vector in human cells is poorly characterized. Using RNA sequencing technology, we compared specific changes in the transcriptomic profiles in human foreskin fibroblast cells following infection by the orf virus. The results indicated that orf virus upregulates or downregulates expression of a variety of genes, including genes involved in antiviral immune response, apoptosis, cell cycle and a series of signaling pathways, such as the IFN and p53-signaling pathways. The orf virus stimulates or inhibits immune gene expression such as chemokines, chemokine receptors, cytokines, cytokine receptors, and molecules involved in antigen uptake and processing after infection. Expression of pro-apoptotic genes increased at 8 hours post-infection. The p53 signaling pathway was activated to induce apoptosis at the same time. However, the cell cycle program was promoted after infection, which may be due to the immunomodulatory genes of the orf virus. This presents the first description of transcription profile changes in human foreskin fibroblast cells after orf virus infection and provides an in-depth analysis of the interaction between the host and orf virus. These data offer new insights into the understanding of the mechanisms of infection by orf virus and identify potential targets for future studies.

show abstract

“…Therefore, we used a similar approach as reported before to monitor the Myt1 kinase activity 9 . Recombinant GST-Cdk1 was incubated with full-length Myt1 and ATP in the presence or absence of GGL1 (30 mg/ml).…”

Section: Resultsmentioning

confidence: 99%

“…However, the assay by Zhou et al was run in a direct instead of a competitive approach using a fluorescently labelled Cdk1-derived peptide substrate. Interestingly, two independent reports suggest that Myt1 does not accept short Cdk1derived peptides as substrates 9,17 . For this reason, Kristjánsdóttir and Rudolph had to use a protein substrate instead of a peptide substrate for their final Myt1 assay 17 .…”

Section: Resultsmentioning

confidence: 99%

“…That report gained a lot of attention and several research groups, including ours, synthesized and derivatized the compound for further biological evaluation [4][5][6][7][8] . However, presumably caused by the restrictive substrate acceptance of this kinase 9 , reliable assay data confirming the original report and elucidating the mechanism of action are still missing.…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

The glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol is no inhibitor of the human Myt1 kinase

Rohe

Göllner

Erdmann

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Previously, a glycoglycerolipid isolated from marine algae was reported to be a potent and selective inhibitor of the human Myt1 kinase, an enzyme involved in cell cycle regulation with great potential as an anti-cancer target. Based on that report, a lot of research effort has been invested by several working groups to synthesize and derivatize this compound. However, reliable assay data confirming the inhibitory potential and the mechanism of action of these glycoglycerolipids are missing so far. Here, based on experimental data and theoretical considerations, we show that the aforesaid glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-d-glucosyl)-sn-glycerol is not an inhibitor of the human Myt1 kinase.

show abstract

In vitro and in silico studies on substrate recognition and acceptance of human PKMYT1, a Cdk1 inhibitory kinase

Cited by 17 publications

References 14 publications

Identification and Pharmacological Inactivation of the MYCN Gene Network as a Therapeutic Strategy for Neuroblastic Tumor Cells

Identification and Pharmacological Inactivation of the MYCN Gene Network as a Therapeutic Strategy for Neuroblastic Tumor Cells

Transcriptomic profiles of human foreskin fibroblast cells in response to orf virus

The glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol is no inhibitor of the human Myt1 kinase

Contact Info

Product

Resources

About