Proto-oncogene serine/threonine-protein kinase

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Revision as of 09:19, 23 July 2024

spinqualitylabelsall models Pim-1 complex with consensus peptide, inhibitor and Cl- ion 3cy2 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights 5 pim-1 3D structures Function Proto-oncogene serine/threonine-protein kinase (Pim1) is the provirus integration site for Moloney murine leukemia virus 1[1]. Pim1 is involved in cell cycle progression, apoptosis, transcriptional activation and signaling pathways. Pim1 phosphorylates and inhibits proapoptotic proteins. For details see Student Project 6 for UMass Chemistry 423 Spring 2015. See also Oncogenes & Tumor Suppressor Genes. Chk1 or checkpoint kinase 1 phosphorylates variety of proteins resulting in activation of DNA damage checkpoint and more[2]. Chk2 or checkpoint kinase 2 has a role in cell cycle arrest and apoptosis by DNA damage [3]. Plk1 or Polo-like kinase 1 phosphorylates variety of proteins affecting cell entry into mitosis, centrosome maturation, spindle assembly and cytokinesis[4]. Plk3 or Polo-like kinase 3 becomes phosphorylated after DNA damage or mitotic spindle disruption [5]. Haspin phosphorylates histone H3 and thus affects mitosis [6]. mTOR or mechanistic target of rapamycin signaling influences longevity and aging [7]. Relevance Pim1 is a progression marker in diffuse large B-cell lymphoma[8]. Disease Pim-1 plays a pivotal role in several tumor relevant signaling pathways and is relevant to colon carcinoma[9]. Structural highlights Pim1 is phosphorylated on serine 261 (PSer). The [10]. Water molecules are shown as red spheres. pim-1 3D structures Serine/threonine protein kinase 3D structures

References

1. ↑ Bachmann M, Moroy T. The serine/threonine kinase Pim-1. Int J Biochem Cell Biol. 2005 Apr;37(4):726-30. PMID:15694833 doi:http://dx.doi.org/10.1016/j.biocel.2004.11.005
2. ↑ Patil M, Pabla N, Dong Z. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci. 2013 Nov;70(21):4009-21. PMID:23508805 doi:10.1007/s00018-013-1307-3
3. ↑ Ahn J, Urist M, Prives C. The Chk2 protein kinase. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1039-47. PMID:15279791 doi:10.1016/j.dnarep.2004.03.033
4. ↑ Iliaki S, Beyaert R, Afonina IS. Polo-like kinase 1 (PLK1) signaling in cancer and beyond. Biochem Pharmacol. 2021 Nov;193:114747. PMID:34454931 doi:10.1016/j.bcp.2021.114747
5. ↑ Bahassi el M, Conn CW, Myer DL, Hennigan RF, McGowan CH, Sanchez Y, Stambrook PJ. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene. 2002 Sep 26;21(43):6633-40. PMID:12242661 doi:10.1038/sj.onc.1205850
6. ↑ Kestav K, Uri A, Lavogina D. Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin. Curr Med Chem. 2017;24(21):2276-2293. PMID:28413956 doi:10.2174/0929867324666170414155520
7. ↑ Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127-134. PMID:29190625 doi:10.1159/000484629
8. ↑ Brault L, Menter T, Obermann EC, Knapp S, Thommen S, Schwaller J, Tzankov A. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma. Br J Cancer. 2012 Jul 24;107(3):491-500. doi: 10.1038/bjc.2012.272. Epub 2012 Jun, 21. PMID:22722314 doi:http://dx.doi.org/10.1038/bjc.2012.272
9. ↑ Weirauch U, Beckmann N, Thomas M, Grunweller A, Huber K, Bracher F, Hartmann RK, Aigner A. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Neoplasia. 2013 Jul;15(7):783-94. PMID:23814490
10. ↑ Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F. 7,8-Dichloro-1-oxo-beta-carbolines as a Versatile Scaffold for the Development of Potent and Selective Kinase Inhibitors with Unusual Binding Modes. J Med Chem. 2012 Jan 12;55(1):403-13. Epub 2012 Jan 3. PMID:22136433 doi:10.1021/jm201286z