B-Raf autoinhibition in the presence and absence of 14-3-3

Abraham, 2000, Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation, J. Biol. Chem., 275, 22300, 10.1074/jbc.M003259200 Agianian, 2018, Current insights of BRAF inhibitors in cancer, J. Med. Chem., 61, 5775, 10.1021/acs.jmedchem.7b01306 Brooks, 2009, CHARMM: the biomolecular simulation program, J. Comput. Chem., 30, 1545, 10.1002/jcc.21287 Bum-Erdene, 2020, Small-molecule covalent bond formation at tyrosine creates a binding site and inhibits activation of Ral GTPases, Proc. Natl. Acad. Sci. U S A, 117, 7131, 10.1073/pnas.1913654117 Chong, 2003, Regulation of Raf through phosphorylation and N terminus-C terminus interaction, J. Biol. Chem., 278, 36269, 10.1074/jbc.M212803200 Clark, 1997, 14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1 cysteine-rich domain, J. Biol. Chem., 272, 20990, 10.1074/jbc.272.34.20990 Cotto-Rios, 2020, Inhibitors of BRAF dimers using an allosteric site, Nat. Commun., 11, 4370, 10.1038/s41467-020-18123-2 Cutler, 1998, Autoregulation of the Raf-1 serine/threonine kinase, Proc. Natl. Acad. Sci. U S A, 95, 9214, 10.1073/pnas.95.16.9214 Daub, 1998, The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes which control Ras-dependent Raf activation, Mol. Cell. Biol., 18, 6698, 10.1128/MCB.18.11.6698 Davies, 2002, Mutations of the BRAF gene in human cancer, Nature, 417, 949, 10.1038/nature00766 DeLano, 2002 Dhillon, 2002, Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of serine 259, Mol. Cell. Biol., 22, 3237, 10.1128/MCB.22.10.3237-3246.2002 Durrant, 2018, Targeting the Raf kinases in human cancer: the Raf dimer dilemma, Br. J. Cancer, 118, 3, 10.1038/bjc.2017.399 Fetics, 2015, Allosteric effects of the oncogenic RasQ61L mutant on Raf-RBD, Structure, 23, 505, 10.1016/j.str.2014.12.017 Flaherty, 2010, Inhibition of mutated, activated BRAF in metastatic melanoma, N. Engl. J. Med., 363, 809, 10.1056/NEJMoa1002011 Fu, 1994, Interaction of the protein kinase Raf-1 with 14-3-3 proteins, Science, 266, 126, 10.1126/science.7939632 Garcia-Gomez, 2018, Protein-protein interactions: emerging oncotargets in the RAS-ERK pathway, Trends Cancer, 4, 616, 10.1016/j.trecan.2018.07.002 Gardino, 2006, Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms, Semin. Cancer Biol., 16, 173, 10.1016/j.semcancer.2006.03.007 Ghosh, 1994, The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras, J. Biol. Chem., 269, 10000, 10.1016/S0021-9258(17)36981-8 Haling, 2014, Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling, Cancer Cell, 26, 402, 10.1016/j.ccr.2014.07.007 Hatzivassiliou, 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers, Nature, 501, 232, 10.1038/nature12441 Holderfield, 2014, Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond, Nat. Rev. Cancer, 14, 455, 10.1038/nrc3760 Hu, 2013, Allosteric activation of functionally asymmetric RAF kinase dimers, Cell, 154, 1036, 10.1016/j.cell.2013.07.046 Humphrey, 1996, VMD: visual molecular dynamics, J. Mol. Graph., 14, 27 Improta-Brears, 1999, Mutational analysis of Raf-1 cysteine rich domain: requirement for a cluster of basic aminoacids for interaction with phosphatidylserine, Mol. Cell. Biochem., 198, 171, 10.1023/A:1006981411691 Karoulia, 2017, New perspectives for targeting RAF kinase in human cancer, Nat. Rev. Cancer, 17, 676, 10.1038/nrc.2017.79 Kohler, 2016, B-Raf activation loop phosphorylation revisited, Cell Cycle, 15, 1171, 10.1080/15384101.2016.1159111 Kondo, 2019, Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases, Science, 366, 109, 10.1126/science.aay0543 Lavoie, 2015, Regulation of RAF protein kinases in ERK signalling, Nat. Rev. Mol. Cell. Biol., 16, 281, 10.1038/nrm3979 Lavoie, 2013, Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization, Nat. Chem. Biol., 9, 428, 10.1038/nchembio.1257 Li, 2018, Raf-1 cysteine-rich domain increases the affinity of K-Ras/Raf at the membrane, promoting MAPK signaling, Structure, 26, 513, 10.1016/j.str.2018.01.011 Liau, 2020, Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization, Nat. Struct. Mol. Biol., 27, 134, 10.1038/s41594-019-0365-0 Lu, 2016, Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view, Chem. Soc. Rev., 45, 4929, 10.1039/C5CS00911A Lu, 2016, Ras conformational ensembles, allostery, and signaling, Chem. Rev., 116, 6607, 10.1021/acs.chemrev.5b00542 Michaud, 1995, 14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner, Mol. Cell. Biol., 15, 3390, 10.1128/MCB.15.6.3390 Molzan, 2010, Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling, Mol. Cell. Biol., 30, 4698, 10.1128/MCB.01636-09 Morrison, 1993, Identification of the major phosphorylation sites of the Raf-1 kinase, J. Biol. Chem., 268, 17309, 10.1016/S0021-9258(19)85336-X Mott, 1996, The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site, Proc. Natl. Acad. Sci. U S A, 93, 8312, 10.1073/pnas.93.16.8312 Nussinov, 2015, Oligomerization and nanocluster organization render specificity, Biol. Rev. Camb. Philos. Soc., 90, 587, 10.1111/brv.12124 Nussinov, 2017, Intrinsic protein disorder in oncogenic KRAS signaling, Cell. Mol. Life Sci., 74, 3245, 10.1007/s00018-017-2564-3 Nussinov, 2019, Does ras activate raf and PI3K allosterically?, Front. Oncol., 9, 1231, 10.3389/fonc.2019.01231 Nussinov, 2019, Is nanoclustering essential for all oncogenic KRas pathways? Can it explain why wild-type KRas can inhibit its oncogenic variant?, Semin. Cancer Biol., 54, 114, 10.1016/j.semcancer.2018.01.002 Nussinov, 2020, Autoinhibition can identify rare driver mutations and advise pharmacology, FASEB J., 34, 16, 10.1096/fj.201901341R Nussinov, 2018, Autoinhibition in Ras effectors Raf, PI3Kalpha, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention, Biophys. Rev., 10, 1263, 10.1007/s12551-018-0461-0 Ostrem, 2013, K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions, Nature, 503, 548, 10.1038/nature12796 Pantsar, 2020, The current understanding of KRAS protein structure and dynamics, Comput. Struct. Biotechnol. J., 18, 189, 10.1016/j.csbj.2019.12.004 Park, 2019, Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes, Nature, 575, 545, 10.1038/s41586-019-1660-y Phillips, 2005, Scalable molecular dynamics with NAMD, J. Comput. Chem., 26, 1781, 10.1002/jcc.20289 Rajakulendran, 2009, A dimerization-dependent mechanism drives RAF catalytic activation, Nature, 461, 542, 10.1038/nature08314 Romano, 2014, Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling, Nat. Cell Biol., 16, 673, 10.1038/ncb2986 Roskoski, 2018, Targeting oncogenic Raf protein-serine/threonine kinases in human cancers, Pharmacol. Res., 135, 239, 10.1016/j.phrs.2018.08.013 Rushworth, 2006, Regulation and role of Raf-1/B-Raf heterodimerization, Mol. Cell. Biol., 26, 2262, 10.1128/MCB.26.6.2262-2272.2006 Shan, 2014, Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase, Nat. Struct. Mol. Biol., 21, 579, 10.1038/nsmb.2849 Shaw, 2014, Kinases and pseudokinases: lessons from RAF, Mol. Cell. Biol., 34, 1538, 10.1128/MCB.00057-14 Shen, 2013, Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation, Mol. Cell, 52, 161, 10.1016/j.molcel.2013.08.044 Stanton, 1987, Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences, Mol. Cell. Biol., 7, 1171 Terrell, 2019, Ras-mediated activation of the raf family kinases, Cold Spring Harb. Perspect. Med., 9, a033746, 10.1101/cshperspect.a033746 Thevakumaran, 2015, Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation, Nat. Struct. Mol. Biol., 22, 37, 10.1038/nsmb.2924 Thorson, 1998, 14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity, Mol. Cell. Biol., 18, 5229, 10.1128/MCB.18.9.5229 Tran, 2005, B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms, J. Biol. Chem., 280, 16244, 10.1074/jbc.M501185200 Travers, 2018, Molecular recognition of RAS/RAF complex at the membrane: role of RAF cysteine-rich domain, Sci. Rep., 8, 8461, 10.1038/s41598-018-26832-4 Tsai, 2018, Allosteric activation of RAF in the MAPK signaling pathway, Curr. Opin. Struct. Biol., 53, 100, 10.1016/j.sbi.2018.07.007 Wan, 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF, Cell, 116, 855, 10.1016/S0092-8674(04)00215-6 Weber, 2001, Active Ras induces heterodimerization of cRaf and BRaf, Cancer Res., 61, 3595 Yaeger, 2019, Targeting alterations in the RAF-MEK pathway, Cancer Discov., 9, 329, 10.1158/2159-8290.CD-18-1321 Zhang, 2000, Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601, EMBO J., 19, 5429, 10.1093/emboj/19.20.5429 Zimmermann, 1999, Phosphorylation and regulation of Raf by Akt (protein kinase B), Science, 286, 1741, 10.1126/science.286.5445.1741