| 1. |
- Johnson, Graham T., et al.
(författare)
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Building the next generation of virtual cells to understand cellular biology
- 2023
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 122:18, s. 3560-3569
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Tidskriftsartikel (refereegranskat)abstract
- Cell science has made significant progress by focusing on understanding individual cellular processes through reductionist approaches. However, the sheer volume of knowledge collected presents challenges in integrating this information across different scales of space and time to comprehend cellular behaviors, as well as making the data and methods more accessible for the community to tackle complex biological questions. This perspective proposes the creation of next-generation virtual cells, which are dynamic 3D models that integrate information from diverse sources, including simulations, biophysical models, image-based models, and evidence-based knowledge graphs. These virtual cells would provide statistically accurate and holistic views of real cells, bridging the gap between theoretical concepts and experimental data, and facilitating productive new collaborations among researchers across related fields.
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| 2. |
- Stebbins, John L., et al.
(författare)
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Identification of a new JNK inhibitor targeting the JNK-JIP interaction site
- 2008
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - 0027-8424 .- 1091-6490. ; 105:43, s. 16809-16813
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Tidskriftsartikel (refereegranskat)abstract
- NK is a stress-activated protein kinase that modulates pathways implicated in a variety of disease states. JNK-interacting protein-1 (JIP1) is a scaffolding protein that enhances JNK signaling by creating a proximity effect between JNK and upstream kinases. A minimal peptide region derived from JIP1 is able to inhibit JNK activity both in vitro and in cell. We report here a series of small molecules JIP1 mimics that function as substrate competitive inhibitors of JNK. One such compound, BI-78D3, dose-dependently inhibits the phosphorylation of JNK substrates both in vitro and in cell. In animal studies, BI-78D3 not only blocks JNK dependent Con A-induced liver damage but also restores insulin sensitivity in mouse models of type 2 diabetes. Our findings open the way for the development of protein kinase inhibitors targeting substrate specific docking sites, rather than the highly conserved ATP binding sites. In view of its favorable inhibition profile, selectivity, and ability to function in the cellular milieu and in vivo, BI-78D3 represents not only a JNK inhibitor, but also a promising stepping stone toward the development of an innovative class of therapeutics.
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