An interconnected hierarchical model of cell death regulation by the BCL-2 family
Open accessAbstract
Multidomain pro-apoptotic BAX and BAK, once activated, permeabilize mitochondria to trigger apoptosis, whereas anti-apoptotic BCL-2 members preserve mitochondrial integrity. The BH3-only molecules (BH3s) promote apoptosis by either activating BAX-BAK or inactivating anti-apoptotic members. Here, we present biochemical and genetic evidence that NOXA is a bona fide activator BH3. Using combinatorial gain-of-function and loss-of-function approaches in Bid(-/-)Bim(-/-)Puma(-/-)Noxa(-/-) and Bax(-/-)Bak(-/-) cells, we have constructed an interconnected hierarchical model that accommodates and explains how the intricate interplays between the BCL-2 members dictate cellular survival versus death. BID, BIM, PUMA and NOXA directly induce stepwise, bimodal activation of BAX-BAK. BCL-2, BCL-XL and MCL-1 inhibit both modes of BAX-BAK activation by sequestering activator BH3s and 'BH3-exposed' monomers of BAX-BAK, respectively. Furthermore, autoactivation of BAX and BAK can occur independently of activator BH3s through downregulation of BCL-2, BCL-XL and MCL-1. Our studies lay a foundation for targeting the BCL-2 family for treating diseases with dysregulated apoptosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Overexpression of BH3-only sensitizers induces minimal apoptosis in cells lacking BID, BIM, PUMA, and NOXA, suggesting that BH3-only activators function downstream of BH3-only sensitizers.
“However, overexpression of BH3-only sensitizers induces minimal apoptosis in cells lacking BID, BIM, PUMA, and NOXA [64], suggesting that BH3-only activators function downstream of BH3-only sensitizers.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [64]
BAX and BAK can self-activate in the absence of anti-apoptotic BCL2 family members and pro-apoptotic BH3 proteins (according to a relatively slow kinetics).
“This observation is in line with the notion that BAX and BAK can self-activate in the absence of anti-apoptotic BCL2 family members and pro-apoptotic BH3 proteins (according to a relatively slow kinetics) [64, 93].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [64]
BID, BIM, PUMA, and NOXA share the ability to physically interact with the mitochondrial pool of BAX and/or BAK to promote conformational changes culminating with dissociation of the core and latch domains of BCL2 effectors.
“BID, BIM, PUMA, and NOXA share the ability to physically (but transiently) interact with the mitochondrial pool of BAX and/or BAK (hence being known as “activators”) to promote a series of conformational changes [59, 64, 67, 71–74] culminating with the dissociation of the core and latch domains of BCL2 effectors [75–77].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [64]
Most pro-survival BCL2 family members inhibit BAX and BAK by preventing their oligomerization and pore-forming activity either directly, upon physical sequestration at the OMM, or indirectly, following the sequestration of BH3-only activators.
“Thus, most pro-survival BCL2 family members inhibit BAX and BAK by preventing their oligomerization and pore-forming activity either directly, upon physical sequestration at the OMM, or indirectly, following the sequestration of BH3-only activators [29, 64, 79, 110].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [64]
Transformed cells lacking all major BH3 activators (BID, BIM, PUMA, and NOXA) can still undergo apoptosis in response to DNA-damaging agents or downregulation of BCL2, BCL-XL, and MCL1.
“However, transformed cells lacking all major BH3 activators (i.e., BID, BIM, PUMA, and NOXA) can still undergo apoptosis in response to DNA-damaging agents or downregulation of BCL2, BCL-XL, and MCL1 [64].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The BCL-2 protein family: opposing activities that mediate cell death
Youle, R. J., & Strasser, A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2308 · Cited by 4,704 · see citing works
Proapoptotic 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
Self-citationBCL-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
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407 · see citing works
Control 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
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058 · see citing works
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
Lowe, S. W., Ruley, H. E., Jacks, T., & Housman, D. E. (1993) · Cell · doi:10.1016/0092-8674(93)90719-7 · Cited by 2,911 · see citing works
(2001) · PubMed · Cited by 2,381 · see citing works
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992 · see citing works
Chen, L., Willis, S. N., Wei, A., Smith, B. J., Fletcher, J. I., Hinds, M. G., Colman, P. M., Day, C. L., Adams, J. M., & Huang, D. C. S. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.030 · Cited by 1,816 · see citing works
Cheng, 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
Self-citationLetai, 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
Structure 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
BAX and BAK Regulation of Endoplasmic Reticulum Ca 2+ : A Control Point for Apoptosis
Scorrano, L., Oakes, S. A., Opferman, J. T., Cheng, E. H. Y., Sorcinelli, M. D., Pozzan, T., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1081208 · Cited by 1,387 · see citing works
Self-citationMitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics
Martinou, J., & Youle, R. J. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.017 · Cited by 1,366 · 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
p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa
Villunger, A., Michalak, E. M., Coultas, L., Müllauer, F., Böck, G., Ausserlechner, M. J., Adams, J. M., & Strasser, A. (2003) · Science · doi:10.1126/science.1090072 · Cited by 1,327 · see citing works
Certo, M. V., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S. J., Armstrong, S. A., & Letai, A. G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.027 · Cited by 1,290 · 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
tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome cPreprint
Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., & Korsmeyer, S. J. (2000) · Genes & Development · doi:10.1101/gad.14.16.2060 · Cited by 1,265 · see citing works
Desagher, S., Osen‐Sand, A., Nichols, A. C., Eskes, R., Montessuit, S., Lauper, S., Maundrell, K., Antonsson, B. E., & Martinou, J. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.5.891 · Cited by 1,260 · see citing works
Willis, S. N., Chen, L., Dewson, G., Wei, A. H., Naik, E., Fletcher, J. I., Adams, J. M., & Huang, D. C. S. (2005) · Genes & Development · doi:10.1101/gad.1304105 · Cited by 1,236 · see citing works
Kuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.003 · Cited by 1,185 · see citing works
Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak
Willis, S. N., Fletcher, J. I., Kaufmann, T., van Delft, M. F., Chen, L., Czabotar, P. E., Ierino, H., Lee, E. F., Fairlie, W. D., Bouillet, P., et al. (2007) · Science · doi:10.1126/science.1133289 · Cited by 1,125 · see citing works
Hierarchical 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
Self-citationVDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis
Cheng, E. H.-Y., Sheiko, T. V., Fisher, J. K., Craigen, W. J., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1083995 · Cited by 852 · see citing works
Self-citationBAX 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
Self-citationBcl-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
Stepwise 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
Self-citationCzabotar, 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
Lovell, J. F., Billen, L. P., Bindner, S., Shamas‐Din, A., Fradin, C., Leber, B. F., & Andrews, D. W. (2008) · Cell · doi:10.1016/j.cell.2008.11.010 · Cited by 565 · see citing works
Molecular biology of Bax and Bak activation and action
Westphal, D., Dewson, G., Czabotar, P. E., & Kluck, R. M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.12.019 · Cited by 518 · see citing works
BID, BIM, and PUMA Are Essential for Activation of the BAX- and BAK-Dependent Cell Death Program
Ren, D., Tu, H.-C., Kim, H., Wang, G. X., Bean, G. R., Takeuchi, O., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J.-D., & Cheng, E. H. Y. (2010) · Science · doi:10.1126/science.1190217 · Cited by 475 · see citing works
Self-citationBax-independent inhibition of apoptosis by Bcl-XL
Cheng, E. H. Y., Levine, B., Boise, L., Thompson, C. B., & Hardwick, J. M. (1996) · Nature · doi:10.1038/379554a0 · Cited by 474 · see citing works
Self-citationStructural insights into the degradation of Mcl-1 induced by BH3 domains
Czabotar, P. E., Lee, E. F., van Delft, M. F., Day, C. L., Smith, B. J., Huang, D. C. S., Fairlie, W. D., Hinds, M. G., & Colman, P. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701297104 · Cited by 449 · see citing works
Westphal, D., Kluck, R. M., & Dewson, G. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.139 · Cited by 437 · see citing works
To Trigger Apoptosis, Bak Exposes Its BH3 Domain and Homodimerizes via BH3:Groove Interactions
Dewson, G., Kratina, T., Sim, H. W., Puthalakath, H., Adams, J. M., Colman, P. M., & Kluck, R. M. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.005 · Cited by 348 · see citing works
Integral role of Noxa in p53-mediated apoptotic responsePreprint
Shibue, T., Takeda, K., Oda, E., Tanaka, H., Murasawa, H., Takaoka, A., Morishita, Y., Akira, S., Taniguchi, T., & Tanaka, N. (2003) · Genes & Development · doi:10.1101/gad.1103603 · Cited by 338 · 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
Self-citationTargeting the B-Cell Lymphoma/Leukemia 2 Family in Cancer
Davids, M. S., & Letai, A. G. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.37.0981 · Cited by 260 · see citing works
Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease
Takeuchi, O., Fisher, J. K., Suh, H., Harada, H., Malynn, B. A., & Korsmeyer, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504783102 · Cited by 203 · 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
BID-induced structural changes in BAK promote apoptosis
Moldoveanu, T., Grace, C. R., Llambi, F., Nourse, A., Fitzgerald, P., Gehring, K., Kriwacki, R. W., & Green, D. R. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2563 · Cited by 201 · see citing works
Proteolysis of MLL family proteins is essential for Taspase1-orchestrated cell cycle progressionPreprint
Takeda, S., Chen, D. Y., Westergard, T. D., Fisher, J. K., Rubens, J. A., Sasagawa, S., Kan, J. T., Korsmeyer, S. J., Cheng, E. H. Y., & Hsieh, J. J.-D. (2006) · Genes & Development · doi:10.1101/gad.1449406 · Cited by 171 · see citing works
Self-citationBH3 Domains other than Bim and Bid Can Directly Activate Bax/Bak
Du, H., Wolf, J., Schafer, B., Moldoveanu, T., Chipuk, J. E., & Kuwana, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.167148 · Cited by 167 · see citing works
Brouwer, J. M., Westphal, D., Dewson, G., Robin, A. Y., Uren, R. T., Bartolo, R., Thompson, G. V., Colman, P. M., Kluck, R. M., & Czabotar, P. E. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.07.016 · Cited by 161 · 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
Direct activation of full-length proapoptotic BAK
Leshchiner, E. S., Braun, C. R., Bird, G. H., & Walensky, L. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214313110 · Cited by 157 · see citing works
Targeting BCL2 for the Treatment of Lymphoid Malignancies
Anderson, M. A., Huang, D. C. S., & Roberts, A. W. (2014) · Seminars in Hematology · doi:10.1053/j.seminhematol.2014.05.008 · Cited by 150 · see citing works
The p53-cathepsin axis cooperates with ROS to activate programmed necrotic death upon DNA damage
Tu, H.-C., Ren, D., Wang, G. X., Chen, D. Y., Westergard, T. D., Kim, H., Sasagawa, S., Hsieh, J. J.-D., & Cheng, E. H. Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808173106 · Cited by 122 · see citing works
Self-citationNaik, E., Michalak, E. M., Villunger, A., Adams, J. M., & Strasser, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200608070 · Cited by 121 · see citing works
Multimodal Interaction with BCL-2 Family Proteins Underlies the Proapoptotic Activity of PUMA BH3
Edwards, A., Gavathiotis, E., LaBelle, J. L., Braun, C. R., Opoku-Nsiah, K., Bird, G. H., & Walensky, L. D. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.06.007 · Cited by 68 · see citing works
Self-citationFu, N. Y., Sukumaran, S. K., Kerk, S. Y., & Yu, V. C. K. (2009) · Molecular Cell · doi:10.1016/j.molcel.2008.11.025 · Cited by 59 · see citing works
From Mitochondrial Biology to Magic Bullet: Navitoclax Disarms BCL-2 in Chronic Lymphocytic Leukemia
Walensky, L. D. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.37.9339 · Cited by 36 · 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-citationMitochondria—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
O'Neill, K. L., Huang, K., Zhang, J., Chen, Y., & Luo, X. (2016) · Genes & Development · doi:10.1101/gad.276725.115 · Cited by 323 · see citing works
Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis
Hirsova, P., Ibrabim, S. H., Gores, G. J., & Malhi, H. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066357 · Cited by 270 · 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
An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway
Garner, T. P., Reyna, D. E., Priyadarshi, A., Chen, H.-C., Li, S., Wu, Y., Ganesan, Y. T., Malashkevich, V. N., Cheng, E. H., & Gavathiotis, E. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.06.010 · Cited by 108 · see citing works
Self-citationCrosstalk between apoptosis and autophagy signaling pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2020.01.003 · Cited by 92 · 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
The Incomplete Puzzle of the BCL2 Proteins
Flores-Romero, H., & García-Sáez, A. J. (2019) · Cells · doi:10.3390/cells8101176 · Cited by 38 · see citing works
MOAP-1 Mediates Fas-Induced Apoptosis in Liver by Facilitating tBid Recruitment to Mitochondria
Tan, C. T., Zhou, Q.-L., Su, Y.-C., Fu, N. Y., Chang, H.-C., Tao, R. N., Sukumaran, S. K., Baksh, S., Tan, Y.-J., Sabapathy, K., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.068 · Cited by 35 · see citing works
Functional investigations of p53 acetylation enabled by heterobifunctional molecules
Chen, L.-Y., Singha Roy, S. J., Jadhav, A. M., Wang, W. W., Chen, P.-H., Bishop, T., Erb, M. A., & Parker, C. G. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00438 · Cited by 18 · see citing works
- Authors
- 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., Ganesan, Y. T., Liao, C.-P., Gavathiotis, E., Hsieh, J. J., & Cheng, E. H.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Chicago (US)
- Stony Brook University (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Cheng, Emily H.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2015-09-07
- Volume
- 17
- Issue
- 10
- Pages
- 1270-1281
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4589531
- OpenAlex
- W1810630981
- Cited by
- 249
- References
- 56
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 21 · 2023: 22 · 2022: 28 · 2021: 17 · 2020: 29 · 2019: 35 · 2018: 26 · 2017: 26 · 2016: 28 · 2015: 1
- FWCI
- 11.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA178394, R01CA125562, P30CA008748, P30CA013330)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bcl-2 family proteins, apoptosis regulation, Bax, Bak, Noxa, BH3-only proteins, mitochondrial membrane permeabilization, Bcl-2, Bcl-xL, Mcl-1, Bid, building information modeling, PUMA, cell death
- MeSH terms
- Bcl-2-Like Protein 11, Animals, Cells, Cultured, Embryo, Mammalian, Fibroblasts, Intestine, Small, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Models, Biological, Proto-Oncogene Proteins, Immunoblotting, Apoptosis, Mice, Knockout, Proto-Oncogene Proteins c-bcl-2, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, RNA Interference, Cytochromes c, bcl-2 Homologous Antagonist-Killer Protein, Apoptosis Regulatory Proteins, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X 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
