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KRAS protein – structure, activity and role in anticancer therapies
Języki publikacji
Abstrakty
Białko KRAS w formie natywnej występuje w organizmie w formie aktywnej, wiążącej GTP lub nieaktywnej, wiążącej GDP. Formy te podlegają cyklicznym, ściśle regulowanym przemianom, dzięki czemu odgrywa ono kluczową rolę w regulacji szlaków sygnalizacyjnych związanych z proliferacją i przeżywalnością komórek. Jednakże białko to jest jednym z najczęściej mutujących onkogenów rodziny białek RAS, które prowadzą do jego niekontrolowanej nadaktywności, a poszczególne jego mutacje powiązane są z licznymi formami nowotworów, które jeszcze do niedawna traktowane były jako „nieuleczalne”.
The KRAS protein in its native form occurs in the body in anactive form - binding GTP and inactive-binding GDP. These forms are subject to cyclical, tightly regulated transformations, which play a crucial role in regulating signaling pathways related to cell proliferation and survival. However, this protein is one of the most frequently mutating oncogenes of the RAS protein family, which leads to its uncontrolled hyperactivity, and its mutations are associated with numerous forms of cancer that until recently were considered as “incurable”.
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Tom
Strony
56--62
Opis fizyczny
Bibliogr. 39 poz., rys.
Twórcy
autor
- Katedra Chemii Bioorganicznej, Wydział Chemiczny, Politechnika Wrocławska, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Polska
autor
- Politechnika Wrocławska, Wydział Chemiczny
autor
- Katedra Chemii Bioorganicznej, Wydział Chemiczny, Politechnika Wrocławska, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Polska
Bibliografia
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- [24] M. Nagasaka, Y. Li, A. Sukari, S.-H. I. Ou, M. N. Al-Hallak, and A. S. Azmi, “KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?,” Cancer Treat. Rev., vol. 84, Mar. 2020, doi: 10.1016/j.ctrv.2020.101974.
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- [26] D. Filchtinski, O. Sharabi, A. Rüppel, I. R. Vetter, C. Herrmann, and J. M. Shifman, “What Makes Ras an Efficient Molecular Switch: A Computational, Biophysical, and Structural Study of Ras-GDP Interactions with Mutants of Raf,” J. Mol. Biol., vol. 399, no. 3, pp. 422–435, 2010, doi: https://doi.org/10.1016/j.jmb.2010.03.046.
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- [35] T. Pantsar, “KRAS(G12C)–AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations,” Sci. Rep., vol. 10, no. 1, p. 11992, 2020, doi: 10.1038/s41598-020-68950-y.
- [36] T. Pantsar, “The current understanding of KRAS protein structure and dynamics,” Comput. Struct. Biotechnol. J., vol. 18, pp. 189–198, Jan. 2020, doi: 10.1016/j.csbj.2019.12.004.
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- [38] A. R. Issahaku et al., “Characterization of the binding of MRTX1133 as an avenue for the discovery of potential KRASG12D inhibitors for cancer therapy,” Sci. Rep., vol. 12, no. 1, p. 17796, 2022, doi: 10.1038/s41598-022-22668-1.
- [39] D. Tang and R. Kang, “Glimmers of hope for targeting oncogenic KRASG12D,” Cancer Gene Ther., vol. 30, no. 3, pp. 391–393, 2023, doi: 10.1038/s41417-022-00561-3.
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-a33d2b58-601f-42f8-977f-b75b536fe0f2
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