Bcl-XL: A multifunctional anti-apoptotic protein

Pharmacological Research - Tập 151 - Trang 104547 - 2020
Mingxue Li1, Dun Wang1, Jianhua He1, Lixia Chen1, Hua Li1,2
1Wuya College of Innovation, School of Pharmaceutical Engineering, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China
2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

Tài liệu tham khảo

Kerr, 1972, Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics, Br. J. Cancer, 26, 239, 10.1038/bjc.1972.33 Silvestris, 1995, Apoptosis or programmed cell death: regulatory and pathophysiological mechanisms, Ann. Ital. Med. Int., 10, 7 Hetts, 1998, To die or not to die: an overview of apoptosis and its role in disease, JAMA., 279, 300, 10.1001/jama.279.4.300 Tsujimoto, 1985, Involvement of the Bcl-2 gene in human follicular lymphoma, Science., 228, 1440, 10.1126/science.3874430 Tsujimoto, 1984, Cloning of the chromosome breakpoint of neoplastic B cells with the t (14;18) chromosome translocation, Science., 226, 1097, 10.1126/science.6093263 Tsujimoto, 1985, Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t (11;14) chromosome translocation, Nature., 315, 340, 10.1038/315340a0 Cleary, 1985, Nucleotide sequence of a t (14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18, Proc. Natl. Acad. Sci. U.S.A., 82, 7439, 10.1073/pnas.82.21.7439 Jagani, 2016, Antiapoptotic Bcl-2 protein as a potential target for cancer therapy: a mini review, Artif. Cells Nanomed. Biotechnol., 44, 1212, 10.3109/21691401.2015.1019668 Boise, 1993, Bcl-X, a Bcl-2-related gene that functions as a dominant regulator of apoptotic cell death, Cell, 74, 597, 10.1016/0092-8674(93)90508-N Warren, 2019, Bcl-2 family isoforms in apoptosis and cancer, Cell Death Dis., 10, 177, 10.1038/s41419-019-1407-6 Muchmore, 1996, X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death, Nature, 381, 335, 10.1038/381335a0 Aritomi, 1997, Crystal structure of rat Bcl-XL: implications for the function of the Bcl-2 protein family, J. Biol. Chem., 272, 27886, 10.1074/jbc.272.44.27886 Liu, 2003, The structure of a Bcl-XL/Bim fragment complex: implications for Bim function, Immunity, 19, 341, 10.1016/S1074-7613(03)00234-6 Lewis, 2014, Bcl-2 family in inter-organelle modulation of calcium signaling; roles in bioenergetics and cell survival, J. Bioenerg. Biomembr., 46, 1, 10.1007/s10863-013-9527-7 Lee, 2019, The structural biology of Bcl-X, Int. J. Mol. Sci., 20, 2234, 10.3390/ijms20092234 Maity, 2018, Flexibility enables to discriminate between ligands: lessons from structural ensembles of Bcl-XL and Mcl-1, Comput. Biol. Chem., 77, 17, 10.1016/j.compbiolchem.2018.08.007 Gabellini, 2017, Non-canonical roles of Bcl-2 and Bcl-XL proteins: relevance of BH4 domain, Carcinogenesis, 38, 579, 10.1093/carcin/bgx016 Jin, 2005, Overview of cell death signaling pathways, Cancer Biol. Ther., 4, 139, 10.4161/cbt.4.2.1508 de Jong, 2018, Bcl-XL as the most promising Bcl-2 family member in targeted treatment of chondrosarcoma, Oncogenesis, 7, 74, 10.1038/s41389-018-0084-0 Liu, 2014, Effect of Bcl-XL gene expression silenced by RNA interference on invasion of human colorectal cancer cells, J. BUON, 19, 925 Scherr, 2016, Bcl-XL is an oncogenic driver in colorectal cancer, Cell Death Dis., 7, E2342, 10.1038/cddis.2016.233 Shimizu, 2010, The let-7 family of microRNAs inhibits Bcl-XL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma, J. Hepatol., 52, 698, 10.1016/j.jhep.2009.12.024 Hernandez, 2013, Hypoxia inducible factor-1α induces chemoresistance phenotype in non-Hodgkin lymphoma cell line via up-regulation of Bcl-XL, Leuk. Lymphoma, 54, 1048, 10.3109/10428194.2012.733874 Chen, 2012, Increase of the therapeutic effect on non-small-cell lung cancer cells with combination treatment of shRNA against Cyclin D1 and Bcl-XL in vitro, Exp. Ther. Med., 3, 255, 10.3892/etm.2011.381 Lee, 2014, Knockdown of Bcl-XL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells, J. Korean Med. Sci., 29, 1464, 10.3346/jkms.2014.29.11.1464 Lee, 2019, Bcl-XL and Mcl-1 are the key Bcl-2 family proteins in melanoma cell survival, Cell Death Dis., 10, 342, 10.1038/s41419-019-1568-3 Brotin, 2010, Bcl-XL and Mcl-1 constitute pertinent targets in ovarian carcinoma and their concomitant inhibition is sufficient to induce apoptosis, Int. J. Cancer, 126, 885 Varin, 2010, Downregulation of Bcl-XL and Mcl-1 is sufficient to induce cell death in mesothelioma cells highly refractory to conventional chemotherapy, Carcinogenesis, 31, 984, 10.1093/carcin/bgq026 Duan, 2018, Co-delivery of Aurora-A inhibitor XY-4 and Bcl-XL siRNA enhances antitumor efficacy for melanoma therapy, Int. J. Nanomed. Nanosurg., 13, 1443, 10.2147/IJN.S147759 Melkko, 2010, Isolation of a small-molecule inhibitor of the antiapoptotic protein Bcl-XL from a DNA-encoded chemical library, ChemMedChem., 5, 584, 10.1002/cmdc.200900520 Takei, 2019, siRNA-based drug targeting human Bcl-XL against cancers, Methods Mol. Biol., 1974, 31, 10.1007/978-1-4939-9220-1_3 Ashkenazi, 2017, From basic apoptosis discoveries to advanced selective Bcl-2 family inhibitors, Nat. Rev. Drug Discov., 16, 273, 10.1038/nrd.2016.253 Park, 2008, Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins, J. Med. Chem., 51, 6902, 10.1021/jm800669s Kipps, 2010, Navitoclax (ABT-263) plus fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR): a phase 1 study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), Blood, 118, 3904, 10.1182/blood.V118.21.3904.3904 Kipps, 2015, A phase 2 study of the BH3 mimetic Bcl-2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia, Leuk. Lymphoma, 56, 2826, 10.3109/10428194.2015.1030638 Mason, 2007, Programmed anuclear cell death delimits platelet life span, Cell, 128, 1173, 10.1016/j.cell.2007.01.037 Leslie, 2010, Beyond clotting: the powers of platelets, Science, 328, 562, 10.1126/science.328.5978.562 Davids, 2011, ABT-199: a new hope for selective Bcl-2 inhibition, Cancer Cell, 23, 139, 10.1016/j.ccr.2013.01.018 Wang, 2019, Bevacizumab synergises with the Bcl-2 inhibitor venetoclax to effectively treat B-cell non-Hodgkin’s lymphoma, Eur. J. Haematol., 103, 234, 10.1111/ejh.13279 Zhu, 2019, Co-operation of ABT-199 and gemcitabine in impeding DNA damage repair and inducing cell apoptosis for synergistic therapy of T-cell acute lymphoblastic leukemia, Anticancer Drugs, 30, 138, 10.1097/CAD.0000000000000702 Li, 2019, The Mcl-1-specific inhibitor S63845 acts synergistically with venetoclax/ABT-199 to induce apoptosis in T-cell acute lymphoblastic leukemia cells, Leukemia, 33, 262, 10.1038/s41375-018-0201-2 Souers, 2013, ABT-199, a potent and selective Bcl-2 inhibitor, achieves antitumor activity while sparing platelets, Nat. Med., 19, 202, 10.1038/nm.3048 Vandenberg, 2013, ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia, Blood., 121, 2285, 10.1182/blood-2013-01-475855 Debrincat, 2015, Bcl-2 is dispensable for thrombopoiesis and platelet survival, Cell Death Dis., 6, E1721, 10.1038/cddis.2015.97 Tao, 2014, Discovery of a potent and selective Bcl-XL inhibitor with in vivo activity, ACS Med. Chem. Lett., 5, 1088, 10.1021/ml5001867 Liu, 2019, Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2, Elife, 8, E37689, 10.7554/eLife.37689 Baruah, 2016, Dynamic Bcl-XL (S49) and (S62) phosphorylation/dephosphorylation during mitosis prevents chromosome instability and aneuploidy in normal human diploid fibroblasts, PLoS One, 11, 10.1371/journal.pone.0159091 Wang, 2014, Phospho-Bcl-XL (Ser62) influences spindle assembly and chromosome segregation during mitosis, Cell Cycle, 13, 1313, 10.4161/cc.28293 Choi, 2016, Bcl-XL promotes metastasis independent of its anti-apoptotic activity, Nat. Commun., 7, 10384, 10.1038/ncomms10384 Byrd, 1999, Depsipeptide (FR901228): a novel therapeutic agent with selective, in vitro activity against human B-cell chronic lymphocytic leukemia cells, Blood, 94, 1401, 10.1182/blood.V94.4.1401 Khan, 2004, Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma, Br. J. Haematol., 125, 156, 10.1111/j.1365-2141.2004.04882.x Delia, 1995, Regulation of apoptosis by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated Bcl-2, Blood, 85, 359, 10.1182/blood.V85.2.359.359 Wei, 2010, BI-97C1, an optically pure apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins, J. Med. Chem., 53, 4166, 10.1021/jm1001265 Arnold, 2008, Preclinical studies of apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in follicular small cleaved cell lymphoma model, Mol. Cancer, 7, 20, 10.1186/1476-4598-7-20 Bruncko, 2007, Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-XL, J. Med. Chem., 50, 641, 10.1021/jm061152t Tse, 2008, ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor, Cancer Res., 68, 3421, 10.1158/0008-5472.CAN-07-5836 Nguyen, 2007, Small molecule obatoclax (GX15-070) antagonizes Mcl-1 and overcomes Mcl-1-mediated resistance to apoptosis, Proc. Natl. Acad. Sci. U.S.A., 104, 19512, 10.1073/pnas.0709443104 Oliver, 2004, In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells, Clin. Cancer Res., 10, 7757, 10.1158/1078-0432.CCR-04-0551 Baggstrom, 2011, A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer, J. Thorac. Oncol., 6, 1757, 10.1097/JTO.0b013e31822e2941 Shoemaker, 2006, A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo, Cancer Res., 66, 8731, 10.1158/0008-5472.CAN-06-0367 Wang, 2006, Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins, J. Med. Chem., 49, 6139, 10.1021/jm060460o Doshi, 2006, Structure-activity relationship studies of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA 14-1), an antagonist for antiapoptotic Bcl-2 proteins to overcome drug resistance in cancer, J. Med. Chem., 49, 7731, 10.1021/jm060968r Tao, 2014, Discovery of a potent and selective Bcl-XL inhibitor with in vivo activity, ACS Med. Chem. Lett., 5, 1088, 10.1021/ml5001867 Zhu, 2017, New agents that target senescent cells: the flavone, fisetin, and the Bcl-X inhibitors, A1331852 and A1155463, Aging, 9, 955, 10.18632/aging.101202 Lessene, 2013, Structure-guided design of a selective Bcl-XL inhibitor, Nat. Chem. Biol., 9, 390, 10.1038/nchembio.1246 Teicher, 2000, Molecular targets and cancer therapeutics: discovery, development and clinical validation, Drug Resist. Updat., 3, 67, 10.1054/drup.2000.0123 Huang, 2000, Bcl-2 family proteins as targets for anticancer drug design, Oncogene, 19, 6627, 10.1038/sj.onc.1204087 Loriot, 2014, Radiosensitization by a novel Bcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer, Cell Death Dis., 5, E1423, 10.1038/cddis.2014.365 Bai, 2014, BM-1197: a novel and specific Bcl-2/Bcl-XL inhibitor inducing complete and long-lasting tumor regression in vivo, PLoS One, 9, E99404, 10.1371/journal.pone.0099404 Aguilar, 2013, A potent and highly efficacious Bcl-2/Bcl-XL inhibitor, J. Med. Chem., 56, 3048, 10.1021/jm4001105 Gozuacik, 2004, Autophagy as a cell death and tumor suppressor mechanism, Oncogene, 23, 2891, 10.1038/sj.onc.1207521 Klionsky, 2000, Autophagy as a regulated pathway of cellular degradation, Science, 290, 1717, 10.1126/science.290.5497.1717 Anglade, 1997, Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease, Histol. Histopathol., 12, 25 New, 2019, Autophagy-dependent secretion: mechanism, factors secreted, and disease implications, Autophagy, 15, 1682, 10.1080/15548627.2019.1596479 Mathew, 2007, Role of autophagy in cancer, Nat. Rev. Cancer, 7, 961, 10.1038/nrc2254 Liang, 1999, Induction of autophagy and inhibition of tumorigenesis by Beclin 1, Nature, 402, 672, 10.1038/45257 Wirawan, 2010, Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria, Cell Death Dis., 1, E18, 10.1038/cddis.2009.16 Mergny, 2010, Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1, Oncogene, 29, 1717, 10.1038/onc.2009.519 Zhu, 2010, Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis, Protein Cell, 1, 468, 10.1007/s13238-010-0048-4 Pattingre, 2005, Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy, Cell, 122, 927, 10.1016/j.cell.2005.07.002 Zhou, 2011, Bcl-2 and Bcl-XL play important roles in the crosstalk between autophagy and apoptosis, FEBS J., 278, 403, 10.1111/j.1742-4658.2010.07965.x Maiuri, 2007, Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1, EMBO J., 26, 2527, 10.1038/sj.emboj.7601689 Pimkina, 2009, ARF induces autophagy by virtue of interaction with Bcl-XL, J. Biol. Chem., 284, 2803, 10.1074/jbc.M804705200 Zalckvar, 2009, DAP-kinase-mediated phosphorylation on the BH3 domain of Beclin 1 promotes dissociation of Beclin 1 from Bcl-XL and induction of autophagy, EMBO Rep., 10, 285, 10.1038/embor.2008.246 Matsuda, 2015, Hypercapnia inhibits autophagy and bacterial killing in human macrophages by increasing expression of Bcl-2 and Bcl-XL, J. Immunol., 194, 5388, 10.4049/jimmunol.1500150 Nakajima, 2017, Bcl-XL affects Group A Streptococcus-induced autophagy directly, by inhibiting fusion between autophagosomes and lysosomes, and indirectly, by inhibiting bacterial internalization via interaction with Beclin 1-UVRAG, PLoS One, 12, 10.1371/journal.pone.0170138 Jonas, 2006, Bcl-XL regulates synaptic plasticity, Mol. Interv., 6, 208, 10.1124/mi.6.4.7 Jonas, 2014, Bcl-XL in neuroprotection and plasticity, Front. Physiol., 5, 355, 10.3389/fphys.2014.00355 Park, 2014, Mitochondrial membrane protein Bcl-XL, a regulator of adult neuronal growth and synaptic plasticity: multiple functions beyond apoptosis, Neural Regen. Res., 9, 1706, 10.4103/1673-5374.143413 Park, 2015, Bcl-XL is necessary for neurite outgrowth in hippocampal neurons, Antioxid. Redox Signal., 22, 93, 10.1089/ars.2013.5570 Iyer, 2013, Developmental patterns of DR6 in normal human hippocampus and in down syndrome, J. Neurodev. Disord., 5, 10, 10.1186/1866-1955-5-10 Jonas, 2003, Modulation of synaptic transmission by the Bcl-2 family protein Bcl-XL, J. Neurosci., 23, 8423, 10.1523/JNEUROSCI.23-23-08423.2003 Li, 2008, Bcl-XL induces DRP1-dependent synapse formation in cultured hippocampal neurons, Proc. Natl. Acad. Sci. U.S.A., 105, 2169, 10.1073/pnas.0711647105 Li, 2013, A Bcl-XL-DRP1 complex regulates synaptic vesicle membrane dynamics during endocytosis, Nat. Cell Biol., 15, 773, 10.1038/ncb2791 Fogarty, 2018, Mcl-1 and Bcl-XL are essential for survival of the developing nervous system, Cell Death Differ., 26, 1501, 10.1038/s41418-018-0225-1 Song, 2018, Stem cells: a promising candidate to treat neurological disorders, Neural Regen. Res., 13, 1294, 10.4103/1673-5374.235085 Pang, 2017, Neural stem cell transplantation is associated with inhibition of apoptosis, Bcl-XL upregulation, and recovery of neurological function in a rat model of traumatic brain injury, Cell Transplant., 26, 1262, 10.1177/0963689717715168 Anderton, 2012, Co-regulation of survival of motor neuron and Bcl-XL expression: implications for neuroprotection in spinal muscular atrophy, Neuroscience, 220, 228, 10.1016/j.neuroscience.2012.06.042 Shishkina, 2010, Resistance to the development of stress-induced behavioral despair in the forced swim test associated with elevated hippocampal Bcl-XL expression, Behav. Brain Res., 213, 218, 10.1016/j.bbr.2010.05.003 Berezova, 2011, Behavior in the forced-swimming test and expression of BDNF and Bcl-XL genes in the rat brain, Zh Vyssh Nerv Deiat Im I P Pavlova, 61, 332 Shishkina, 2012, Stress-induced activation of the brainstem Bcl-XL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior, Neuropharmacology, 62, 177, 10.1016/j.neuropharm.2011.06.016 Dygalo, 2012, Increased expression of the anti-apoptotic protein Bcl-XL in the brain is associated with resilience to stress-induced depression-like behavior, Cell. Mol. Neurobiol., 32, 767, 10.1007/s10571-011-9794-y Dygalo, 2017, Effects of short-term exposure to lithium on antiapoptotic Bcl-XL protein expression in cortex and hippocampus of rats after acute stress, Biochemistry, 82, 345 Park, 2017, ΔN-Bcl-XL, a therapeutic target for neuroprotection, Neural Regen. Res., 12, 1791, 10.4103/1673-5374.219033 Park, 2017, Inhibition of Bcl-XL prevents pro-death actions of ΔN-Bcl-XL at the mitochondrial inner membrane during glutamate excitotoxicity, Cell Death Differ., 24, 1963, 10.1038/cdd.2017.123 Park, 2019, Vitamin E prevents ΔN-Bcl-XL-associate mitochondrial dysfunction in primary hippocampal neurons (P14-024-19), Curr Dev Nutr., 3 Stumpf, 2019, Lycopene protects cortical neurons via oxidative stress-mediated ΔN-Bcl-XL formation (FS05-08-19), Curr Dev Nutr., 3 Park, 2018, Nutritional regulators of Bcl-XL in the brain, Molecules, 23, E3019, 10.3390/molecules23113019 Kasahara, 2014, Mitochondria: from cell death executioners to regulators of cell differentiation, Trends Cell Biol., 24, 761, 10.1016/j.tcb.2014.08.005 Lan, 2019, The roles of mitochondria-associated membranes in mitochondrial quality control under endoplasmic reticulum stress, Life Sci., 231, 116587, 10.1016/j.lfs.2019.116587 Lee, 2018, The interface between ER and mitochondria: molecular compositions and functions, Mol. Cells, 41, 1000 Chen, 2011, Bcl-XL regulates mitochondrial energetics by stabilizing the inner membrane potential, J. Cell Biol., 195, 263, 10.1083/jcb.201108059 Tagami, 2000, A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity, Oncogene, 19, 5736, 10.1038/sj.onc.1203948 Williams, 2016, The non-apoptotic action of Bcl-XL: regulating Ca2+ signaling and bioenergetics at the ER-mitochondrion interface, J. Bioenerg. Biomembr., 48, 211, 10.1007/s10863-016-9664-x Monaco, 2012, Selective regulation of IP3-receptor-mediated Ca2+ signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-XL, Cell Death Differ., 19, 295, 10.1038/cdd.2011.97 Eno, 2012, Distinct roles of mitochondria- and ER-localized Bcl-XL in apoptosis resistance and Ca2+ homeostasis, Mol. Biol. Cell, 23, 2605, 10.1091/mbc.e12-02-0090 Huang, 2013, An interaction between Bcl-XL and the voltage-dependent anion channel (VDAC) promotes mitochondrial Ca2+ uptake, J. Biol. Chem., 288, 19870, 10.1074/jbc.M112.448290 Vervliet, 2017, Modulation of Ca2+ signaling by anti-apoptotic B-cell lymphoma 2 proteins at the endoplasmic reticulum-mitochondrial interface, Front. Oncol., 7, 75, 10.3389/fonc.2017.00075 Jonas, 2014, Contributions of Bcl-XL to acute and long term changes in bioenergetics during neuronal plasticity, Biochim. Biophys. Acta, 1842, 1168, 10.1016/j.bbadis.2013.11.007 Alavian, 2011, Bcl-XL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase, Nat. Cell Biol., 13, 1224, 10.1038/ncb2330 Luciani, 2013, Bcl-2 and Bcl-XL suppress glucose signaling in pancreatic β-cells, Diabetes, 62, 170, 10.2337/db11-1464 Thomas, 2009, Beta cell apoptosis in diabetes, Apoptosis, 14, 1389, 10.1007/s10495-009-0339-5 Soria, 2013, Dual trade of Bcl-2 and Bcl-XL in islet physiology, Diabetes, 62, 18, 10.2337/db12-1023 Hughes, 2006, Role of Bim and other Bcl-2 family members in autoimmune and degenerative diseases, Curr. Dir. Autoimmun., 9, 74 Grillot, 1995, Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice, J. Exp. Med., 182, 1973, 10.1084/jem.182.6.1973 Amanna, 2003, Enforced Bcl-XL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice, J. Immunol., 170, 4593, 10.4049/jimmunol.170.9.4593 Sharabi, 2010, Bcl-XL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide, J. Autoimmun., 34, 87, 10.1016/j.jaut.2009.06.002 Chen, 2010, Constitutive expression of Bcl-XL in the T lineage attenuates collagen-induced arthritis in Bcl-XL transgenic mice, Arthritis Rheum., 46, 514, 10.1002/art.10128 Haque, 2010, FoxP3 and Bcl-XL cooperatively promote regulatory T cell persistence and prevention of arthritis development, Arthritis Res. Ther., 12, R66, 10.1186/ar2983 Sharabi, 2010, Bcl-XL affects the development of functional CD4 tregs, Arthritis Res. Ther., 12, 405, 10.1186/ar3076 Qiao, 2016, Imbalanced expression of Bcl-XL and Bax in platelets treated with plasma from immune thrombocytopenia, Immunol. Res., 64, 604, 10.1007/s12026-015-8760-z Jones, 2017, Senescence is not inevitable, Biogerontology, 18, 965, 10.1007/s10522-017-9727-3 Zhu, 2015, The achilles’ heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell, 14, 644, 10.1111/acel.12344 Rochette, 2008, Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein Bcl-XL, Mech. Ageing Dev., 129, 207, 10.1016/j.mad.2007.12.007 Geiger, 2016, Depleting senescent cells to combat aging, Nat. Med., 22, 23, 10.1038/nm.4024 Yosef, 2016, Directed elimination of senescent cells by inhibition of Bcl-W and Bcl-XL, Nat. Commun., 7, 11190, 10.1038/ncomms11190 Pignolo, 2019, Exceptional human longevity, Mayo Clin. Proc., 94, 110, 10.1016/j.mayocp.2018.10.005 Borras, 2015, Centenarians overexpress Bcl-XL, which confers them a protection against apoptosis, oxidative stress and immunosenescence, Free Radic. Biol. Med., 86, S11, 10.1016/j.freeradbiomed.2015.07.051 Borras, 2016, Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-XL in successful aging, Aging, 8, 3185, 10.18632/aging.101078 Leverson, 2015, Exploiting selective Bcl-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy, Sci. Transl. Med., 7, 279ra40, 10.1126/scitranslmed.aaa4642