Is Nanoclustering essential for all oncogenic KRas pathways? Can it explain why wild-type KRas can inhibit its oncogenic variant?

Seminars in Cancer Biology - Tập 54 - Trang 114-120 - 2019
Ruth Nussinov1,2, Chung‐Jung Tsai1, Hyunbum Jang1
1Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA
2Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

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Villalonga, 2001, Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling, Mol. Cell. Biol., 21, 7345, 10.1128/MCB.21.21.7345-7354.2001

Chavan, 2015, High-affinity interaction of the K-Ras4B hypervariable region with the ras active site, Biophys. J ., 109, 2602, 10.1016/j.bpj.2015.09.034

Liao, 2016, RASSF5: An, MST activator and tumor suppressor in vivo but opposite in vitro, Curr. Opin. Struct. Biol., 41, 217, 10.1016/j.sbi.2016.09.001

Sperlich, 2016, Regulation of K-Ras4B membrane binding by calmodulin, Biophys. J ., 111, 113, 10.1016/j.bpj.2016.05.042

Jang, 2017, Flexible-body motions of calmodulin and the farnesylated hypervariable region yield a high-affinity interaction enabling K-Ras4B membrane extraction, J. Biol. Chem., 292, 12544, 10.1074/jbc.M117.785063

Ni, 2013, Structural basis for autoactivation of human Mst2 kinase and its regulation by RASSF5, Structure, 21, 1757, 10.1016/j.str.2013.07.008

Tsai, 2015, K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif, Proc. Natl. Acad. Sci. U. S. A., 112, 779, 10.1073/pnas.1412811112

Muratcioglu, 2017, PDEδ binding to ras isoforms provides a route to proper membrane localization, J. Phys. Chem. B, 121, 5917, 10.1021/acs.jpcb.7b03035

Dharmaiah, 2016, Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ, Proc. Natl. Acad. Sci. U. S. A., 113, E6766, 10.1073/pnas.1615316113

Eser, 2014, Oncogenic KRAS signalling in pancreatic cancer, Br. J. Cancer, 111, 817, 10.1038/bjc.2014.215

Bryant, 2014, KRAS: feeding pancreatic cancer proliferation, Trends Biochem. Sci., 39, 91, 10.1016/j.tibs.2013.12.004

Lu, 2016, Ras conformational ensembles, allostery, and signaling, Chem. Rev., 116, 6607, 10.1021/acs.chemrev.5b00542

Jang, 2016, Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ from H-Ras dimers, Biochem. J, 473, 1719, 10.1042/BCJ20160031

Banerjee, 2016, The disordered hypervariable region and the folded catalytic domain of oncogenic K-Ras4B partner in phospholipid binding, Curr. Opin. Struct. Biol., 36, 10, 10.1016/j.sbi.2015.11.010

Jang, 2016, The higher level of complexity of K-Ras4B activation at the membrane, FASEB J., 30, 1643, 10.1096/fj.15-279091

Nan, 2015, Ras-GTP dimers activate the mitogen-activated protein kinase (MAPK) pathway, Proc. Natl. Acad. Sci. U. S. A., 112, 7996, 10.1073/pnas.1509123112

Spencer-Smith, 2017, Targeting the α4-α5 interface of RAS results in multiple levels of inhibition, Small GTPases

Nussinov, 2016, Oncogenic KRAS signaling and YAP1/β-catenin: similar cell cycle control in tumor initiation, Semin. Cell Dev. Biol., 58, 79, 10.1016/j.semcdb.2016.04.001

Nussinov, 2015, Principles of K-Ras effector organization and the role of oncogenic K-Ras in cancer initiation through G1 cell cycle deregulation, Expert Rev. Proteomics., 12, 669, 10.1586/14789450.2015.1100079

Chavan, 2015, Plasma membrane regulates Ras signaling networks, Cell Logist, 5, e1136374, 10.1080/21592799.2015.1136374

Jang, 2015, Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region, J. Biol. Chem., 290, 9465, 10.1074/jbc.M114.620724

Chen, 2016, Ras dimer formation as a new signaling mechanism and potential cancer therapeutic target, Mini Rev. Med. Chem., 16, 391, 10.2174/1389557515666151001152212

Bandaru, 2017, Deconstruction of the Ras switching cycle through saturation mutagenesis, Elife, 6, 10.7554/eLife.27810

Nussinov, 2016, A new view of ras isoforms in cancers, Cancer Res., 76, 18, 10.1158/0008-5472.CAN-15-1536

Chakrabarti, 2016, Comparison of the conformations of KRAS isoforms, K-Ras4A and K-Ras4B, points to similarities and significant differences, J. Phys. Chem. B, 120, 667, 10.1021/acs.jpcb.5b11110

Li, 2017, Computational modeling reveals that signaling lipids modulate the orientation of K-Ras4A at the membrane reflecting protein topology, Structure, 25, 679, 10.1016/j.str.2017.02.007

Tse, 2016, Exploring molecular mechanisms of paradoxical activation in the BRAF kinase dimers: atomistic simulations of conformational dynamics and modeling of allosteric communication networks and signaling pathways, PLoS One, 11, e0166583, 10.1371/journal.pone.0166583

Jain, 2017, CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles, Oncogene, 36, 6348, 10.1038/onc.2017.276

Kubiniok, 2017, Time-resolved phosphoproteome analysis of paradoxical RAF activation reveals novel targets of ERK, Mol. Cell. Proteomics, 16, 663, 10.1074/mcp.M116.065128

Liao, 2017, The dynamic mechanism of RASSF5 and MST kinase activation by Ras, Phys. Chem. Chem. Phys., 19, 6470, 10.1039/C6CP08596B

Nussinov, 2017, Intrinsic protein disorder in oncogenic KRAS signaling, Cell. Mol. Life Sci., 74, 3245, 10.1007/s00018-017-2564-3

Nussinov, 2014, Dynamic multiprotein assemblies shape the spatial structure of cell signaling, Prog. Biophys. Mol. Biol., 116, 158, 10.1016/j.pbiomolbio.2014.07.002

Nussinov, 2015, Oligomerization and nanocluster organization render specificity, Biol. Rev. Camb. Philos. Soc., 90, 587, 10.1111/brv.12124

Avruch, 2012, Protein kinases of the Hippo pathway: regulation and substrates, Semin. Cell Dev. Biol., 23, 770, 10.1016/j.semcdb.2012.07.002

Richter, 2009, The RASSF proteins in cancer; from epigenetic silencing to functional characterization, Biochim. Biophys. Acta, 1796, 114

Avruch, 2009, Rassf family of tumor suppressor polypeptides, J. Biol. Chem., 284, 11001, 10.1074/jbc.R800073200

Donninger, 2016, Ras signaling through RASSF proteins, Semin. Cell Dev. Biol., 58, 86, 10.1016/j.semcdb.2016.06.007

Nussinov, 2017, A new view of pathway-Driven drug resistance in tumor proliferation, Trends Pharmacol. Sci., 38, 427, 10.1016/j.tips.2017.02.001

Nussinov, 2016, Independent and core pathways in oncogenic KRAS signaling, Expert Rev. Proteomics., 13, 711, 10.1080/14789450.2016.1209417

Hwang, 2014, Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway, Acta Crystallogr. D Biol. Crystallogr., 70, 1944, 10.1107/S139900471400947X

Makbul, 2013, Structural and thermodynamic characterization of Nore1-SARAH: a small, helical module important in signal transduction networks, Biochemistry, 52, 1045, 10.1021/bi3014642

Hwang, 2007, Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway, Proc. Natl. Acad. Sci. U. S. A., 104, 9236, 10.1073/pnas.0610716104

Harjes, 2006, GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1, Structure, 14, 881, 10.1016/j.str.2006.03.008

Villalonga, 2002, Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts, J. Biol. Chem., 277, 37929, 10.1074/jbc.M202245200

Agell, 2006, The diverging roles of calmodulin and PKC in the regulation of p21 intracellular localization, ABBV Cell Cycle, 5, 3, 10.4161/cc.5.1.2270

Naguib, 2016, Following the trail of lipids: signals initiated by PI3 K function at multiple cellular membranes, Sci. Signal., 9, re4, 10.1126/scisignal.aad7885

Xia, 2015, PI3 K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application, Am. J. Cancer. Res., 5, 1602

Yang, 2016, New insights on PI3 K/AKT pathway alterations and clinical outcomes in breast cancer, Cancer Treat Rev, 45, 87, 10.1016/j.ctrv.2016.03.004

Mandelker, 2009, A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane, Proc. Natl. Acad. Sci. U. S. A., 106, 16996, 10.1073/pnas.0908444106

Gabelli, 2014, Activation of PI3Kα by physiological effectors and by oncogenic mutations: structural and dynamic effects, Biophys. Rev., 6, 89, 10.1007/s12551-013-0131-1

Burke, 2012, Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α (PIK3CA), Proc. Natl. Acad. Sci. U. S. A., 109, 15259, 10.1073/pnas.1205508109

Berchtold, 2014, The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer, Biochim. Biophys. Acta, 1843, 398, 10.1016/j.bbamcr.2013.10.021

Alvarez-Moya, 2010, K-Ras4 B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function, Oncogene, 29, 5911, 10.1038/onc.2010.298

Wu, 2011, Both the C-terminal polylysine region and the farnesylation of K-RasB are important for its specific interaction with calmodulin, PLoS One, 6, e21929, 10.1371/journal.pone.0021929

Abraham, 2009, The hypervariable region of K-Ras4 B is responsible for its specific interactions with calmodulin, Biochemistry, 48, 7575, 10.1021/bi900769j

Chavan, 2013, Application of reductive 13C-methylation of lysines to enhance the sensitivity of conventional NMR methods, Molecules, 18, 7103, 10.3390/molecules18067103

Nussinov, 2015, The key role of calmodulin in KRAS-Driven adenocarcinomas, Mol. Cancer Res., 13, 1265, 10.1158/1541-7786.MCR-15-0165

Nussinov, 2016, K-Ras4B/calmodulin/PI3Kα: A promising new adenocarcinoma-specific drug target?, Expert Opin. Ther. Targets, 20, 831, 10.1517/14728222.2016.1135131

Joyal, 1997, Calmodulin activates phosphatidylinositol 3-kinase, J. Biol. Chem., 272, 28183, 10.1074/jbc.272.45.28183

Liao, 2006, Growth factor-dependent AKT activation and cell migration requires the function of c-K(B)-Ras versus other cellular ras isoforms, J. Biol. Chem., 281, 29730, 10.1074/jbc.M600668200

Nussinov, 2017, Calmodulin and PI3 K signaling in KRAS cancers trends, Cancer, 3, 214

Lu, 2016, Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view, Chem. Soc. Rev., 45, 4929, 10.1039/C5CS00911A

Harden, 2009, Phospholipase C isozymes as effectors of Ras superfamily GTPases, J. Lipid Res., 50, S243, 10.1194/jlr.R800045-JLR200

Kelley, 2004, Hormonal regulation of phospholipase Cε through distinct and overlapping pathways involving G12 and Ras family G-proteins, Biochem. J, 378, 129, 10.1042/bj20031370

Hains, 2006, Gα12/13- and rho-dependent activation of phospholipase C-ε by lysophosphatidic acid and thrombin receptors, Mol. Pharmacol., 69, 2068, 10.1124/mol.105.017921

Oestreich, 2007, Epac-mediated activation of phospholipase Cε plays a critical role in β-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac myocytes, J. Biol. Chem., 282, 5488, 10.1074/jbc.M608495200

Tidyman, 2009, The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation, Curr. Opin. Genet. Dev., 19, 230, 10.1016/j.gde.2009.04.001

Rauen, 2013, The RASopathies, Annu. Rev. Genomics Hum. Genet., 14, 355, 10.1146/annurev-genom-091212-153523

Tidyman, 2016, Pathogenetics of the RASopathies, Hum. Mol. Genet., 25, R123, 10.1093/hmg/ddw191

Spandidos, 1988, The normal human H-ras1 gene can act as an onco-suppressor, Br. J. Cancer Suppl., 9, 67

Spandidos, 1990, Expression of the normal H-ras1 gene can suppress the transformed and tumorigenic phenotypes induced by mutant ras genes, Anticancer Res., 10, 1543

Zhou, 2016, The role of wild type RAS isoforms in cancer, Semin. Cell Dev. Biol., 58, 60, 10.1016/j.semcdb.2016.07.012

Zhang, 2001, Wildtype Kras2 can inhibit lung carcinogenesis in mice, Nat. Genet., 29, 25, 10.1038/ng721

Staffas, 2015, Wild-type KRAS inhibits oncogenic KRAS-induced T-ALL in mice, Leukemia, 29, 1032, 10.1038/leu.2014.315

Kong, 2016, Loss of wild-type Kras promotes activation of all Ras isoforms in oncogenic Kras-induced leukemogenesis, Leukemia, 30, 1542, 10.1038/leu.2016.40

Qiu, 2011, Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo, Oncotarget, 2, 862, 10.18632/oncotarget.357

Guerrero, 1985, Loss of the normal N-ras allele in a mouse thymic lymphoma induced by a chemical carcinogen, Proc. Natl. Acad. Sci. U. S. A., 82, 7810, 10.1073/pnas.82.23.7810

Diaz, 2002, The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene, Cancer Res., 62, 4514

To, 2013, Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis, Oncogene, 32, 4028, 10.1038/onc.2012.404

Xu, 2013, Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation, Cancer Discov., 3, 993, 10.1158/2159-8290.CD-13-0096

Matallanas, 2011, Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras, Mol. Cell, 44, 893, 10.1016/j.molcel.2011.10.016

Rauch, 2017, Spatial regulation of ARAF controls the MST2-Hippo pathway, Small GTPases, 10, 1, 10.1080/21541248.2017.1288686