BH3 Domains of BH3-Only Proteins Differentially Regulate Bax-Mediated Mitochondrial Membrane Permeabilization Both Directly and Indirectly
Open accessAbstract
Using a Bax-dependent membrane-permeabilization assay, we show that peptides corresponding to the BH3 domains of Bcl-2 family "BH3-only" proteins have dual functions. Several BH3 peptides relieved the inhibition of Bax caused by the antiapoptotic Bcl-x(L) and/or Mcl-1 proteins, some displaying a specificity for either Bcl-x(L) or Mcl-1. Besides having this derepression function, the Bid and Bim peptides activated Bax directly and were the only BH3 peptides tested that could potently induce cytochrome c release from mitochondria in cultured cells. Furthermore, Bax activator molecules (cleaved Bid protein and the Bim BH3 peptide) synergistically induced cytochrome c release when introduced into cells along with derepressor BH3 peptides. These observations support a unified model of BH3 domain function, encompassing both positive and negative regulation of other Bcl-2 family members. In this model, the simple inhibition of antiapoptotic functions is insufficient to induce apoptosis unless a direct activator of Bax or Bak is present.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Upon induction of apoptosis, BAX retrotranslocation ceases as the mitochondrial pools of BAX and BAK undergo direct or indirect activation by pro-apoptotic BH3-only proteins.
“Upon induction of apoptosis, BAX retrotranslocation ceases as the mitochondrial pools of BAX and BAK undergo direct or indirect activation (see below) by pro-apoptotic BH3-only proteins [48, 56–59].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [56]
Cites
1 retracted
Ku70 suppresses the apoptotic translocation of Bax to mitochondria
Sawada, M., Sun, W., Hayes, P. L., Leskov, K., Boothman, D. A., & Matsuyama, S. (2003) · Nature Cell Biology · doi:10.1038/ncb950 · Cited by 353 · see citing works
RetractedProapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988 · see citing works
BCL-2 family members and the mitochondria in apoptosisPreprint
Gross, A., McDonnell, J. M., & Korsmeyer, S. J. (1999) · Genes & Development · doi:10.1101/gad.13.15.1899 · Cited by 3,623 · see citing works
Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death
Yang, E., Zha, J., Jockel, J., Boise, L., Thompson, C. B., & Korsmeyer, S. J. (1995) · Cell · doi:10.1016/0092-8674(95)90411-5 · Cited by 2,101 · see citing works
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
Chipuk, J. E., Kuwana, T., Bouchier-Hayes, L., Droin, N. M., Newmeyer, D. D., Schuler, M., & Green, D. R. (2004) · Science · doi:10.1126/science.1092734 · Cited by 2,066 · cited 2× · see citing works
“For example, family proteins, although regulatory partners outside the family may also be important (Chipuk et al., 2004; Cud-E -Myc tumor cells can undergo apoptosis when Bcl-2 is downregulated (Letai et al., 2004). deback et al., 2001; Guo et al., 2003; Sawada et al., 2003).”
BackgroundSelf-citationCheng, E. H. Y., Wei, M. C., Weiler, S., Flavell, R. A., Mak, T. W., Lindsten, T., & Korsmeyer, S. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00320-3 · Cited by 1,708 · see citing works
Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00127-7 · Cited by 1,677 · see citing works
Lindsten, T., Ross, A. J., King, A., Zong, W.-X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00136-2 · Cited by 1,489 · see citing works
Bid, Bax, and Lipids Cooperate to Form Supramolecular Openings in the Outer Mitochondrial Membrane
Kuwana, T., Mackey, M. R., Perkins, G. A., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R., & Newmeyer, D. D. (2002) · Cell · doi:10.1016/s0092-8674(02)01036-x · Cited by 1,480 · see citing works
Self-citationStructure of Bcl-x <sub>L</sub> -Bak Peptide Complex: Recognition Between Regulators of Apoptosis
Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., et al. (1997) · Science · doi:10.1126/science.275.5302.983 · Cited by 1,476 · see citing works
Yin, X.-M., Oltvai, Z., & Korsmeyer, S. (1994) · Nature · doi:10.1038/369321a0 · Cited by 1,383 · see citing works
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349 · see citing works
Newmeyer, D. D., & Ferguson-Miller, S. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00116-8 · Cited by 1,268 · see citing works
Self-citationEnforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis
Gross, A., Jockel, J., Wei, M. C., & Korsmeyer, S. J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.14.3878 · Cited by 1,086 · see citing works
JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
Lei, K., & Davis, R. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438011100 · Cited by 1,068 · see citing works
Puthalakath, H., Huang, D. C. S., O'REILLY, L. A., King, S. M., & Strasser, A. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80456-6 · Cited by 1,053 · see citing works
BH3-Only Proteins—Essential Initiators of Apoptotic Cell Death
Huang, D. C. S., & Strasser, A. (2000) · Cell · doi:10.1016/s0092-8674(00)00187-2 · Cited by 1,044 · see citing works
Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death.
Korsmeyer, S. J., Shutter, J. R., Novack, D. V., Merry, D. E., & Oltvai, Z. N. (1993) · PubMed · Cited by 865 · see citing works
Multiple Bcl-2 family members demonstrate selective dimerizations with Bax.
Sedlak, T. W., Oltvai, Z. N., Yang, E., Wang, K., Boise, L., Thompson, C. B., & Korsmeyer, S. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7834 · Cited by 816 · see citing works
Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis?
Heiden, M. G. V., & Thompson, C. B. (1999) · Nature Cell Biology · doi:10.1038/70237 · Cited by 659 · see citing works
Molecular Cloning and Characterization of Bif-1
Cuddeback, S. M., Yamaguchi, H., Komatsu, K., Miyashita, T., Yamada, M., Wu, C., Singh, S., & Wang, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101527200 · Cited by 635 · see citing works
Bcl-2-family proteins and the role of mitochondria in apoptosis
Kuwana, T., & Newmeyer, D. D. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.004 · Cited by 625 · see citing works
Self-citationHumanin peptide suppresses apoptosis by interfering with Bax activation
Guo, B., Zhai, D., Cabezas, E., Welsh, K., Nouraini, S., Satterthwait, A. C., & Reed, J. C. (2003) · Nature · doi:10.1038/nature01627 · Cited by 619 · see citing works
Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiationPreprint
Nijhawan, D., Fang, M., Traer, E. A., Zhong, Q., Gao, W., Du, F., & Wang, X. (2003) · Genes & Development · doi:10.1101/gad.1093903 · Cited by 590 · see citing works
Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL
Degterev, A., Lugovskoy, A. A., Cardone, M. H., Mulley, B., Wagner, G., Mitchison, T. J., & Yuan, J. (2001) · Nature Cell Biology · doi:10.1038/35055085 · Cited by 550 · see citing works
Bim is a suppressor of Myc-induced mouse B cell leukemia
Egle, A., Harris, A. W., Bouillet, P., & Cory, S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401471101 · Cited by 482 · see citing works
Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3
Tzung, S.-P., Kim, K. M., Basañez, G., Giedt, C. D., Simon, J., Zimmerberg, J., Zhang, K. Y. J., & Hockenbery, D. M. (2001) · Nature Cell Biology · doi:10.1038/35055095 · Cited by 452 · see citing works
Harada, H., Quearry, B., Ruiz‐Vela, A., & Korsmeyer, S. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406837101 · Cited by 287 · see citing works
Bad Is a BH3 Domain-Containing Protein That Forms an Inactivating Dimer with Bcl-X L
Kelekar, A., Chang, B. S., Harlan, J. E., Fesik, S. W., & Thompson, C. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.12.7040 · Cited by 273 · see citing works
Cartron, P., Gallenne, T., Bougras-Cartron, G., Gautier, F., Manero, F., Vusio, P., Méflah, K., Vallette, F. M., & Juin, P. P. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.10.028 · Cited by 255 · see citing works
Lipidic Pore Formation by the Concerted Action of Proapoptotic BAX and tBID
Terrones, O., Antonsson, B. E., Yamaguchi, H., Wang, H., Liu, J., Lee, R. M., Herrmann, A., & Basáñez, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313420200 · Cited by 243 · see citing works
Yethon, J. A., Epand, R. F., Leber, B. F., Epand, R. M., & Andrews, D. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306289200 · Cited by 203 · see citing works
Antiapoptotic BCL-2 is required for maintenance of a model leukemia
Letai, A. G., Sorcinelli, M. D., Beard, C., & Korsmeyer, S. J. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.011 · Cited by 175 · see citing works
Regulation of apoptosis by BH3 domains in a cell-free system
Cosulich, S. C., Worrall, V., Hedge, P., Green, S., & Clarke, P. R. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00410-6 · Cited by 166 · see citing works
Minimal BH3 Peptides Promote Cell Death by Antagonizing Anti-apoptotic Proteins
Moreau, C., Cartron, P., Hunt, A. E., Méflah, K., Green, D. R., Evan, G. I., Vallette, F. M., & Juin, P. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209472200 · Cited by 89 · see citing works
Self-citationDirect addition of BimL to mitochondria does not lead to cytochrome c release
Terradillos, O., Montessuit, S., Huang, D. C. S., & Martinou, J. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02871-5 · Cited by 46 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationControl of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219 · see citing works
Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
Singh, R., Letai, A., & Sarosiek, K. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0089-8 · Cited by 2,111 · see citing works
BCL-2 family proteins: changing partners in the dance towards death
Kale, J., Osterlund, E. J., & Andrews, D. W. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.186 · Cited by 1,574 · see citing works
How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.169 · Cited by 1,395 · see citing works
Anoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160 · see citing works
Maurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881 · see citing works
Self-citationHierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies
Kim, H., Rafiuddin-Shah, M., Tu, H.-C., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J.-D., & Cheng, E. H.-Y. (2006) · Nature Cell Biology · doi:10.1038/ncb1499 · Cited by 874 · see citing works
Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies
Delbridge, A. R. D., Grabow, S., Strasser, A., & Vaux, D. L. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.17 · Cited by 752 · see citing works
p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis
Vaseva, A. V., Marchenko, N. D., Ji, K., Tsirka, S. E., Holzmann, S., & Moll, U. M. (2012) · Cell · doi:10.1016/j.cell.2012.05.014 · Cited by 740 · see citing works
Mechanisms of Action of Bcl-2 Family Proteins
Shamas-Din, A., Kale, J., Leber, B., & Andrews, D. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008714 · Cited by 705 · see citing works
BAX activation is initiated at a novel interaction site
Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H.-C., Kim, H., Cheng, E. H.-Y., Tjandra, N., et al. (2008) · Nature · doi:10.1038/nature07396 · Cited by 700 · see citing works
Bcl-xL Retrotranslocates Bax from the Mitochondria into the Cytosol
Edlich, F., Banerjee, S., Suzuki, M., Cleland, M. M., Arnoult, D., Wang, C., Neutzner, A., Tjandra, N., & Youle, R. J. (2011) · Cell · doi:10.1016/j.cell.2011.02.034 · Cited by 630 · see citing works
Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario
Chipuk, J. E., Bouchier-Hayes, L., & Green, D. R. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401963 · Cited by 631 · see citing works
Self-citationThe BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics
Hata, A. N., Engelman, J. A., & Faber, A. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0011 · Cited by 619 · see citing works
A Unified Model of Mammalian BCL-2 Protein Family Interactions at the Mitochondria
Llambi, F., Moldoveanu, T., Tait, S. W. G., Bouchier-Hayes, L., Temirov, J., McCormick, L. L., Dillon, C. P., & Green, D. R. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.10.001 · Cited by 596 · see citing works
Self-citationStepwise Activation of BAX and BAK by tBID, BIM, and PUMA Initiates Mitochondrial Apoptosis
Kim, H., Tu, H.-C., Ren, D., Takeuchi, O., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J.-D., & Cheng, E. H.-Y. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.030 · Cited by 600 · see citing works
Czabotar, P. E., Westphal, D., Dewson, G., Ma, S., Hockings, C., Fairlie, W. D., Lee, E. F., Yao, S., Robin, A. Y., Smith, B. J., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.031 · Cited by 573 · see citing works
The BCL-2 arbiters of apoptosis and their growing role as cancer targets
Adams, J. M., & Cory, S. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.161 · Cited by 530 · see citing works
Kurppa, K. J., Liu, Y., To, C., Zhang, T., Fan, M., Vajdi, A., Knelson, E. H., Xie, Y., Lim, K., Cejas, P., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.006 · Cited by 475 · see citing works
Chipuk, J. E., McStay, G. P., Bharti, A., Kuwana, T., Clarke, C. J., Siskind, L. J., Obeid, L. M., & Green, D. R. (2012) · Cell · doi:10.1016/j.cell.2012.01.038 · Cited by 436 · see citing works
Self-citationElgendy, M., Sheridan, C., Brumatti, G., & Martin, S. J. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.009 · Cited by 426 · see citing works
A Stapled BID BH3 Helix Directly Binds and Activates BAX
Walensky, L. D., Pitter, K., Morash, J., Oh, K. J., Barbuto, S., Fisher, J., Smith, E., Verdine, G. L., & Korsmeyer, S. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.020 · Cited by 383 · see citing works
Mitochondria—Judges and Executioners of Cell Death Sentences
Bhola, P. D., & Letai, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.019 · Cited by 326 · see citing works
BH3-Triggered Structural Reorganization Drives the Activation of Proapoptotic BAX
Gavathiotis, E., Reyna, D. E., Davis, M. L., Bird, G. H., & Walensky, L. D. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.019 · Cited by 310 · see citing works
An interconnected hierarchical model of cell death regulation by the BCL-2 family
Chen, H.-C., Kanai, M., Inoue-Yamauchi, A., Tu, H.-C., Huang, Y., Ren, D., Kim, H., Takeda, S., Reyna, D. E., Chan, P. M., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3236 · Cited by 249 · see citing works
Schellenberg, B., Wang, P., Keeble, J. A., Rodriguez-Enriquez, R., Walker, S., Owens, T. W., Foster, F., Tanianis-Hughes, J., Brennan, K., Streuli, C. H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.12.022 · Cited by 237 · see citing works
The BCL-2 family of proteins and mitochondrial outer membrane permeabilisation
Birkinshaw, R. W., & Czabotar, P. E. (2017) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2017.04.001 · Cited by 229 · see citing works
Multisite Phosphorylation Regulates Bim Stability and Apoptotic Activity
Hübner, A., Barrett, T., Flavell, R. A., & Davis, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.025 · Cited by 228 · see citing works
Jiang, X., Jiang, H., Shen, Z., & Wang, X. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417253111 · Cited by 220 · see citing works
Killing cancer cells by flipping the Bcl-2/Bax switch
Cory, S., & Adams, J. M. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.012 · Cited by 217 · see citing works
Mitochondrial Shape Governs BAX-Induced Membrane Permeabilization and Apoptosis
Renault, T. T., Floros, K. V., Elkholi, R., Corrigan, K.-A., Kushnareva, Y., Wieder, S. Y., Lindtner, C., Serasinghe, M. N., Asciolla, J. J., Buettner, C., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.10.028 · Cited by 217 · see citing works
Self-citationCragg, M. S., Jansen, E. S., Cook, M., Harris, C., Strasser, A., & Scott, C. L. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35437 · Cited by 207 · see citing works
Differential retrotranslocation of mitochondrial Bax and Bak
Todt, F., Cakir, Z., Reichenbach, F., Emschermann, F., Lauterwasser, J., Kaiser, A., Ichim, G., Tait, S. W., Frank, S., Langer, H. F., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201488806 · Cited by 172 · see citing works
Walensky, L. D., & Gavathiotis, E. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.08.009 · Cited by 173 · see citing works
Dai, H., Smith, A., Meng, X. W., Schneider, P. A., Pang, Y.-P., & Kaufmann, S. H. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102027 · Cited by 159 · see citing works
Physiological and Pharmacological Control of BAK, BAX, and Beyond
Luna-Vargas, M. P. A., & Chipuk, J. E. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.07.002 · Cited by 142 · see citing works
Self-citationVerhaegen, M., Bauer, J. A., Martín de la Vega, C., Wang, G., Wolter, K. G., Brenner, J. C., Nikolovska-Coleska, Z., Bengtson, A., Nair, R., Elder, J. T., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1748 · Cited by 140 · see citing works
Cunha, D. A., Igoillo-Esteve, M., Gurzov, E. N., Germano, C. M., Naamane, N., Marhfour, I., Fukaya, M., Vanderwinden, J.-M., Gysemans, C., Mathieu, C., et al. (2012) · Diabetes · doi:10.2337/db12-0123 · Cited by 130 · see citing works
Apoptosis induced by proteasome inhibition in cancer cells: predominant role of the p53/PUMA pathway
Concannon, C. G., Koehler, B. F., Reimertz, C., Murphy, B. M., Bonner, C., Thurow, N., Ward, M. W., Villunger, A., Strasser, A., Kögel, D., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1209974 · Cited by 95 · see citing works
Nutlin-3 protects kidney cells during cisplatin therapy by suppressing Bax/Bak activation
Jiang, M., Pabla, N., Murphy, R. F., Yang, T., Yin, X.-M., Degenhardt, K., White, E., & Dong, Z. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m606928200 · Cited by 97 · see citing works
Oh, K. J., Singh, P., Lee, K., Foss, K., Lee, S., Park, M., Lee, S., Aluvila, S., Park, M., Singh, P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135293 · Cited by 87 · see citing works
Crossing paths: interactions between the cell death machinery and growth factor survival signals
Brumatti, G., Salmanidis, M., & Ekert, P. G. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0288-8 · Cited by 85 · see citing works
Bleicken, S., Hantusch, A., Das, K. K., Frickey, T., & Garcia-Saez, A. J. (2017) · Nature Communications · doi:10.1038/s41467-017-00086-6 · Cited by 70 · see citing works
Organization of the Mitochondrial Apoptotic BAK Pore
Aluvila, S., Mandal, T., Hustedt, E., Fajer, P., Choe, J. Y., & Oh, K. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526806 · Cited by 71 · see citing works
Josefsson, E. C., Vainchenker, W., & James, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207591 · Cited by 68 · see citing works
Bok is a genuine multi-BH-domain protein that triggers apoptosis in the absence of Bax and Bak
Einsele-Scholz, S., Malmsheimer, S., Bertram, K., Stehle, D., Johänning, J., Manz, M., Daniel, P. T., Gillissen, B. F., Schulze-Osthoff, K., & Essmann, F. (2016) · Journal of Cell Science · doi:10.1242/jcs.181727 · Cited by 65 · see citing works
Sale, M. J., & Cook, S. J. (2013) · Biochemical Journal · doi:10.1042/bj20121212 · Cited by 58 · see citing works
β-Cell Responses to Nitric Oxide
Broniowska, K. A., Oleson, B. J., & Corbett, J. A. (2014) · Vitamins & Hormones · doi:10.1016/b978-0-12-800174-5.00012-0 · Cited by 48 · see citing works
Genome-wide prediction and validation of peptides that bind human prosurvival Bcl-2 proteins
DeBartolo, J., Taipale, M., & Keating, A. E. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003693 · Cited by 39 · see citing works
Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia
Ridinger-Saison, M., Evanno, E., Gallais, I., Rimmelé, P., Selimoglu-Buet, D., Sapharikas, E., Moreau-Gachelin, F., & Guillouf, C. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.88 · Cited by 34 · see citing works
Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor-induced apoptosis
Xing, Y., Igarashi, H., Wang, X., & Sakaguchi, N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050637 · Cited by 30 · see citing works
Phosphorylation alters Bim‐mediated Mcl‐1 stabilization and priming
Conage‐Pough, J. E., & Boise, L. H. (2018) · The FEBS Journal · doi:10.1111/febs.14505 · Cited by 32 · see citing works
Proapoptotic role of nuclear clusterin in brain
Kim, N., & Choi, W. S. (2011) · Anatomy & Cell Biology · doi:10.5115/acb.2011.44.3.169 · Cited by 29 · see citing works
Luo, L., Yang, J., & Liu, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.583393 · Cited by 18 · see citing works
Mitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2 · see citing works
- Authors
- Kuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D.
- Affiliations
- La Jolla Institute for Immunology (US)
- Corresponding author
- Kuwana, Tomomi
- Newmeyer, Donald D.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 17
- Issue
- 4
- Pages
- 525-535
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2094052642
- Cited by
- 1,185
- References
- 36
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 16 · 2023: 28 · 2022: 25 · 2021: 37 · 2020: 45 · 2019: 42 · 2018: 40 · 2017: 44 · 2016: 57 · 2015: 56 · 2014: 57 · 2013: 76 · 2012: 75
- FWCI
- 38.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R21AG024157)
- National Cancer Institute (CA 69381, P01CA069381)
- National Institute of General Medical Sciences (GM50284, R01GM050284, R01GM062289, GM62289)
- National Institute of Allergy and Infectious Diseases (R01AI040646, AI40646)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- BH3 domain, BH3-only proteins, Bax, mitochondrial membrane permeabilization, Bcl-2 family proteins, Bcl-xL, Mcl-1, Bid, building information modeling, cytochrome c release, apoptosis, Bax activation, anti-apoptotic proteins, Bak
- MeSH terms
- Bcl-2-Like Protein 11, Amino Acid Sequence, Carrier Proteins, HeLa Cells, Humans, Intracellular Membranes, Membrane Proteins, Mitochondria, Molecular Sequence Data, Neoplasm Proteins, Peptide Fragments, Permeability, Proto-Oncogene Proteins, Apoptosis, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Proto-Oncogene Proteins c-bcl-2, Mitochondrial Proteins, Cytochromes c, Apoptosis Regulatory Proteins, bcl-X Protein, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein, Myeloid Cell Leukemia Sequence 1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
