Genomes and Genes
Gene Symbol: Bcl2l1
Description: BCL2-like 1
Alias: Bcl(X)L, Bcl-XL, Bcl2l, BclX, bcl-x, bcl2-L-1, bcl-2-like protein 1, B-cell leukemia/lymphoma x, anti-apoptosis regulatory protein, apoptosis regulator Bcl-X
- Zhang J, Chen Y, Hardwick J, Miller M, Plachez C, Richards L, et al. Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis. J Neurosci. 2005;25:1881-8 pubmed..Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype. ..
- Rucker E, Dierisseau P, Wagner K, Garrett L, Wynshaw Boris A, Flaws J, et al. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol. 2000;14:1038-52 pubmed..These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis. ..
- Hon H, Rucker E, Hennighausen L, Jacob J. bcl-xL is critical for dendritic cell survival in vivo. J Immunol. 2004;173:4425-32 pubmed..Taken together, our work demonstrates that the bcl-x(L) isoform is critical for survival of skin-derived, Ag-bearing DC in vivo. ..
- Zhao B, Song A, Haque R, Lei F, Weiler L, Xiong X, et al. Cooperation between molecular targets of costimulation in promoting T cell persistence and tumor regression. J Immunol. 2009;182:6744-52 pubmed publisher..The data provide new insights into why costimulatory signals might need to be sustained over time and suggest a potential novel approach to augment cellular immunotherapy for cancer. ..
- Carrington E, McKenzie M, Jansen E, Myers M, Fynch S, Kos C, et al. Islet beta-cells deficient in Bcl-xL develop but are abnormally sensitive to apoptotic stimuli. Diabetes. 2009;58:2316-23 pubmed publisher..Bcl-xL expression at physiological levels may partially protect beta-cells from apoptotic stimuli, including apoptosis because of mediators implicated in type 1 diabetes and death or degeneration of transplanted islets. ..
- Cheung W, Kim J, Linden M, Peng L, Van Ness B, Polakiewicz R, et al. Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. J Clin Invest. 2004;113:1763-73 pubmed..Our findings demonstrate that the enforced expression of Myc and Bcl-X(L) by Ig enhancers with peak activity in plasma cells generates a mouse model of human PCN that recapitulates some features of human multiple myeloma. ..
- Haque R, Lei F, Xiong X, Wu Y, Song J. FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. Arthritis Res Ther. 2010;12:R66 pubmed publisher..Our results provide a novel approach for generating highly reactive Tregs for augmenting cellular immunotherapy for autoimmune disease. ..
- Wagner K, Claudio E, Rucker E, Riedlinger G, Broussard C, Schwartzberg P, et al. Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. Development. 2000;127:4949-58 pubmed..Mice conditionally deficient in Bcl-x permitted us for the first time to study the effects of Bcl-x deficiency on cell proliferation, maturation and survival under physiological conditions in an adult animal. ..
- Grillot D, Gonzalez Garcia M, Ekhterae D, Duan L, Inohara N, Ohta S, et al. Genomic organization, promoter region analysis, and chromosome localization of the mouse bcl-x gene. J Immunol. 1997;158:4750-7 pubmed..12 and K562 cell lines. The remarkable similarity between the genomic regions of bcl-2 and bcl-x suggests that these genes have evolved from a common ancestral gene or through gene duplication. ..
- Yang X, Weber G, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity. 1997;7:629-39 pubmed..Identification of Bcl-x gamma helps provide a molecular explanation of T cell activation and death after antigen engagement. ..
- Fang W, Weintraub B, Dunlap B, Garside P, Pape K, Jenkins M, et al. Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity. 1998;9:35-45 pubmed..These studies suggest that Bcl-x may have a distinct role in controlling survival at the immature stage of B cell development and demonstrate that tolerance is preserved when self-reactive B cells escape central deletion. ..
- Jeong S, Gaume B, Lee Y, Hsu Y, Ryu S, Yoon S, et al. Bcl-x(L) sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers. EMBO J. 2004;23:2146-55 pubmed..The C-terminal tail of Bcl-x(L) is also required to mediate Bcl-x(L)/Bax heterodimer formation. Both mitochondrial import and antiapoptotic activity of different Bcl-x(L) mutants correlate with their ability to form homodimers. ..
- Liu X, Dai S, Zhu Y, Marrack P, Kappler J. The structure of a Bcl-xL/Bim fragment complex: implications for Bim function. Immunity. 2003;19:341-52 pubmed..Our results suggest a way in which both Bim and Bax/Bak might be required for activated T cell apoptosis. ..
- Danial N, Walensky L, Zhang C, Choi C, Fisher J, Molina A, et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 2008;14:144-53 pubmed publisher..Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion. ..
- Vikstrom I, Carotta S, Lüthje K, Peperzak V, Jost P, Glaser S, et al. Mcl-1 is essential for germinal center formation and B cell memory. Science. 2010;330:1095-9 pubmed publisher..We investigated the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-x(L)) from B cells using an inducible system synchronized with expression of activation-induced cytidine ..
- Gonzalez Garcia M, PEREZ BALLESTERO R, Ding L, Duan L, Boise L, Thompson C, et al. bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria. Development. 1994;120:3033-42 pubmed..Based on its tissue and developmental patterns of expression, it appears that bcl-x may play an important role in the regulation of cell death during development and tissue homeostasis. ..
- Valks D, Kemp T, Clerk A. Regulation of Bcl-xL expression by H2O2 in cardiac myocytes. J Biol Chem. 2003;278:25542-7 pubmed..These data demonstrate that the Bcl-x gene is selectively responsive to oxidative stress, and the response is mediated through distal promoter regions. ..
- Zhu Y, Swanson B, Wang M, Hildeman D, Schaefer B, Liu X, et al. Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells. Proc Natl Acad Sci U S A. 2004;101:7681-6 pubmed..Our results indicate that, in T cells, Bim function is regulated by interaction with Bcl-2 family members on mitochondria rather than by sequestration to the microtubules. ..
- Chen Y, Aon M, Hsu Y, Soane L, Teng X, McCaffery J, et al. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. J Cell Biol. 2011;195:263-76 pubmed publisher..Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins. ..
- Naik P, Karrim J, Hanahan D. The rise and fall of apoptosis during multistage tumorigenesis: down-modulation contributes to tumor progression from angiogenic progenitors. Genes Dev. 1996;10:2105-16 pubmed..Thus, down-modulation of apoptosis selectively contributes to late steps in a tumorigenesis pathway. ..
- Grillot D, Merino R, Nunez G. 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. 1995;182:1973-83 pubmed..In contrast to Bcl-2, which has been implicated in the maintenance of mature T cells, Bcl-xL appears to provide a survival signal for the maintenance of more immature CD4+CD8+ thymocytes before positive selection. ..
- Motoyama N, Wang F, Roth K, Sawa H, Nakayama K, Negishi I, et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science. 1995;267:1506-10 pubmed..The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems. ..
- Heermeier K, Benedict M, Li M, Furth P, Nunez G, Hennighausen L. Bax and Bcl-xs are induced at the onset of apoptosis in involuting mammary epithelial cells. Mech Dev. 1996;56:197-207 pubmed..These findings point to a significant role for Bax and Bcl-xS in the regulation of apoptosis of secretory alveolar cells during involution. ..
- Chao D, Linette G, Boise L, White L, Thompson C, Korsmeyer S. Bcl-XL and Bcl-2 repress a common pathway of cell death. J Exp Med. 1995;182:821-8 pubmed..Immunoprecipitation indicated that Bcl-xL, like Bcl-2, heterodimerized with the death-promoting molecule Bax in thymocytes. This in vivo model argues that Bcl-xL, like Bcl-2, functions in a common pathway to repress cell death. ..
- Choi M, Holmann M, Atkins C, Klaus G. Expression of bcl-x during mouse B cell differentiation and following activation by various stimuli. Eur J Immunol. 1996;26:676-82 pubmed
- Rhodes M, Kopsombut P, Bondurant M, Price J, Koury M. Bcl-x(L) prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin. Blood. 2005;106:1857-63 pubmed..Bcl-x(L) is not required for heme synthesis and does not mediate the antiapoptotic effects of erythropoietin, but it prevents ineffective erythropoiesis due to apoptosis in late-stage, hemoglobin-synthesizing erythroblasts. ..
- Berman S, Chen Y, Qi B, McCaffery J, Rucker E, Goebbels S, et al. Bcl-x L increases mitochondrial fission, fusion, and biomass in neurons. J Cell Biol. 2009;184:707-19 pubmed publisher..Deficits in these Bcl-x(L)-dependent mechanisms may be critical in neuronal dysfunction during the earliest phases of neurodegeneration, long before commitment to cell death. ..
- Gauthier E, Piche L, Lemieux G, Lemieux R. Role of bcl-X(L) in the control of apoptosis in murine myeloma cells. Cancer Res. 1996;56:1451-6 pubmed
- Grillot D, Merino R, Pena J, Fanslow W, Finkelman F, Thompson C, et al. bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J Exp Med. 1996;183:381-91 pubmed..Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation. ..
- Kodama T, Hikita H, Kawaguchi T, Shigekawa M, Shimizu S, Hayashi Y, et al. Mcl-1 and Bcl-xL regulate Bak/Bax-dependent apoptosis of the megakaryocytic lineage at multistages. Cell Death Differ. 2012;19:1856-69 pubmed publisher..In conclusion, Mcl-1 and Bcl-xL regulate the survival of the megakaryocytic lineage, which is critically important for preventing lethal or severe hemorrhage in both developing and adult mice. ..
- Henderson C, Zhang Z, Manson S, Riehm J, Kataoka M, Flye M, et al. A moderate reduction of Bcl-x(L) expression protects against tumorigenesis; however, it also increases susceptibility to tissue injury. Oncogene. 2005;24:7120-4 pubmed..Additionally, they indicate that the potential for increased susceptibility to tissue injury must be considered in the design of chemopreventative and antineoplastic strategies that involve inhibition of Bcl-x(L) activity. ..
- Gross A, McDonnell J, Korsmeyer S. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899-911 pubmed
- Djerbi M, Malinowski M, Yagita H, Zhivotovsky B, Grandien A. Participation of FLIP, RIP and Bcl-x(L) in Fas-mediated T-cell death. Scand J Immunol. 2007;66:410-21 pubmed..These results indicate that yet uncharacterized signalling pathways from the Fas receptor are critically involved in lymphoproliferative and autoimmune disease observed in lpr mice and autoimmune lymphoproliferative syndrome patients. ..
- Kodama T, Takehara T, Hikita H, Shimizu S, Shigekawa M, Li W, et al. BH3-only activator proteins Bid and Bim are dispensable for Bak/Bax-dependent thrombocyte apoptosis induced by Bcl-xL deficiency: molecular requisites for the mitochondrial pathway to apoptosis in platelets. J Biol Chem. 2011;286:13905-13 pubmed publisher..Despite residing in platelets, BH3-only activator proteins Bid and Bim are dispensable for Bax activation and mitochondrial apoptosis. ..
- Fang W, Mueller D, Pennell C, Rivard J, Li Y, Hardy R, et al. Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene. Immunity. 1996;4:291-9 pubmed..This analysis also demonstrated that immunoglobulin gene rearrangement is less precise than previously appreciated. ..
- Akhtar R, Klocke B, Strasser A, Roth K. Loss of BH3-only protein Bim inhibits apoptosis of hemopoietic cells in the fetal liver and male germ cells but not neuronal cells in bcl-x-deficient mice. J Histochem Cytochem. 2008;56:921-7 pubmed publisher..Our work identifies Bim as an important regulator of bcl-x deficiency-induced cell death during hematopoiesis and testicular development. ..
- Zhou Y, Pena J, Roe M, Mittal A, Levisetti M, Baldwin A, et al. Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion. Am J Physiol Endocrinol Metab. 2000;278:E340-51 pubmed
- Pierson W, Cauwe B, Policheni A, Schlenner S, Franckaert D, Berges J, et al. Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3? regulatory T cells. Nat Immunol. 2013;14:959-65 pubmed publisher..Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways. ..
- Wang K, Yin X, Chao D, Milliman C, Korsmeyer S. BID: a novel BH3 domain-only death agonist. Genes Dev. 1996;10:2859-69 pubmed..This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX. ..
- O CONNOR L, Strasser A, O Reilly L, Hausmann G, Adams J, Cory S, et al. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998;17:384-95 pubmed..Hence, Bim appears to act as a 'death ligand' which can only neutralize certain members of the pro-survival Bcl-2 sub-family. ..
- Peperzak V, Vikstrom I, Walker J, Glaser S, Lepage M, Coquery C, et al. Mcl-1 is essential for the survival of plasma cells. Nat Immunol. 2013;14:290-7 pubmed publisher..Our results identify a critical role for Mcl-1 in the maintenance of plasma cells...
- Willis S, Chen L, Dewson G, Wei A, Naik E, Fletcher J, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19:1294-305 pubmed..The finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the Bcl-2 family. ..
- Zhao R, Oxley D, Smith T, Follows G, Green A, Alexander D. DNA damage-induced Bcl-xL deamidation is mediated by NHE-1 antiport regulated intracellular pH. PLoS Biol. 2007;5:e1 pubmed..Our findings also suggest novel approaches to cancer therapy. ..
- Takehara T, Tatsumi T, Suzuki T, Rucker E, Hennighausen L, Jinushi M, et al. Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology. 2004;127:1189-97 pubmed..Furthermore, it offers proof that persistent apoptosis of parenchymal cells is sufficient to induce fibrotic responses and suggests a mechanistic link between apoptosis and fibrosis. ..
- Walton K, Wagner K, Rucker E, Shillingford J, Miyoshi K, Hennighausen L. Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. Mech Dev. 2001;109:281-93 pubmed..Concomitant deletion of the bax gene did not significantly modify the Bcl-x phenotype. Our results suggest that Bcl-x is not essential during mammopoiesis, but is critical for controlled apoptosis during the first phase of involution. ..
- Danial N, Gramm C, Scorrano L, Zhang C, Krauss S, Ranger A, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature. 2003;424:952-6 pubmed..This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis. ..
- Brown F, Scott N, Rank G, Collinge J, Vadolas J, Vickaryous N, et al. ENU mutagenesis identifies the first mouse mutants reproducing human ?-thalassemia at the genomic level. Blood Cells Mol Dis. 2013;50:86-92 pubmed publisher..The RBC13 and RBC14 lines are the first ?-thalassemia mouse models that reproduce human ?-thalassemia at the genomic level, and as such highlight the power of ENU mutagenesis screens in generating mouse models of human disease. ..
- Chang J, Ryang Y, Kim S, Park J. Trichomonas vaginalis-induced apoptosis in RAW264.7 cells is regulated through Bcl-xL, but not Bcl-2. Parasite Immunol. 2004;26:141-50 pubmed..vaginalis. Therefore, these results suggest that T. vaginalis-induced apoptosis in RAW264.7 cells can occur via a Bcl-x(L)-dependent apoptotic mechanism. ..
- Elsegood C, Chang M, Jessup W, Scholz G, Hamilton J. Glucose metabolism is required for oxidized LDL-induced macrophage survival: role of PI3K and Bcl-2 family proteins. Arterioscler Thromb Vasc Biol. 2009;29:1283-9 pubmed publisher..These results suggest that oxLDL enhances macrophage survival in the absence of CSF-1 by inducing PI3K-dependent glucose uptake, which is metabolized to maintain Bcl-2 and Bcl-x(L) protein levels. ..
- Fujinaka Y, Takane K, Yamashita H, Vasavada R. Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation. J Biol Chem. 2007;282:30707-17 pubmed..We believe this is the first direct demonstration of lactogens mediating their protective effect through the JAK2/STAT5 pathway in the beta cell and through Bcl-XL in any cell type. ..
- Joseph R, Li T. Overexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration. Invest Ophthalmol Vis Sci. 1996;37:2434-46 pubmed..Cell death pathways not regulated by Bcl-2 may be operative in photoreceptor degeneration. ..
- Wang X, Rao R, Kosakowska Cholody T, Masood M, Southon E, Zhang H, et al. Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice. J Cell Biol. 2009;184:143-58 pubmed publisher..Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways. ..
- Uesaka T, Enomoto H. Neural precursor death is central to the pathogenesis of intestinal aganglionosis in Ret hypomorphic mice. J Neurosci. 2010;30:5211-8 pubmed publisher..These results indicate that ENCC death is a principal cause of intestinal aganglionosis in a Ret hypomorphic state, and suggest that the inhibition of cell death is a route to the prevention of HSCR. ..
- Cordell P, Kile B, Standeven K, Josefsson E, Pease R, Grant P. Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion. Blood. 2010;115:2674-81 pubmed publisher..Hence, this mechanism may precede FXIII-A release into the extracellular matrix from macrophages and its release into plasma from the cell type of origin. ..
- Kodama T, Hikita H, Kawaguchi T, Saito Y, Tanaka S, Shigekawa M, et al. The Bcl-2 homology domain 3 (BH3)-only proteins Bim and bid are functionally active and restrained by anti-apoptotic Bcl-2 family proteins in healthy liver. J Biol Chem. 2013;288:30009-18 pubmed publisher..Hepatocyte integrity is maintained by the dynamic and well orchestrated Bcl-2 network in the healthy liver. ..
- Wang Z, Karras J, Howard R, Rothstein T. Induction of bcl-x by CD40 engagement rescues sIg-induced apoptosis in murine B cells. J Immunol. 1995;155:3722-5 pubmed..This result suggests that the up-regulation of bcl-x by CD40L plays an important role in CD40-mediated apoptotic rescue in murine B cells. ..
- Savitt J, Jang S, Mu W, Dawson V, Dawson T. Bcl-x is required for proper development of the mouse substantia nigra. J Neurosci. 2005;25:6721-8 pubmed..Surprisingly, surviving neurons were found that lacked Bcl-x immunoreactivity, thereby demonstrating that this gene is dispensable for the ongoing survival of a subpopulation of catecholaminergic cells. ..