Bcl2l1

..These results have relevance for therapies in a wide variety of progressive retinal and neuronal degenerations where Ca(2+) overload, lead exposure, andor mitochondrial dysfunction occur...

..Furthermore, we demonstrate that Mcl-1 functions together with Bcl-xL to promote double-positive thymocyte survival. Thus, Mcl-1 is a critical anti-apoptotic factor for the survival of T cells at multiple stages in vivo...

..Natural complexes of Siva-1/BCL-X(L) are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis...

..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 ..

..Mcl-1 and Bcl-xL are two major anti-apoptotic Bcl-2 family proteins expressed in the liver and cooperatively control hepatic integrity during liver development and in adult liver homeostasis in a gene dose-dependent manner...

..BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-X(L)...

..Both genes were demonstrated to be direct transcriptional targets of Stat5. This establishes an unexpected mechanistic link between EpoR/Jak/Stat signaling and iron metabolism, processes absolutely essential for erythropoiesis and life...

..These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis...

..However, prominent cell death of bcl-x-/- EryP and EryD occurred when the cells matured. The data show that the antiapoptotic function of bcl-x acts at the very end of erythroid maturation...

..The aim of this study was to explore the function of Bcl-xL in hepatocytes using the Cre-loxP system and to analyze the consequences of long-term apoptosis in hepatocytes...

..Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype...

..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...

..These results indicate that Bcl-x is dispensable for the generation of effector and memory T lymphocytes and suggest that costimulation of T lymphocytes promotes their survival through a Bcl-x(L) independent mechanism...

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..Taken together, our work demonstrates that the bcl-x(L) isoform is critical for survival of skin-derived, Ag-bearing DC in vivo...

..These results suggest that even under non-apoptotic conditions, expression of Bcl-2-family proteins influences a signaling network that links changes in mitochondrial metabolism to alterations in nuclear gene expression...

..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...

..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...

..These data suggest a role for Bcl-XL during in vitro midbrain DA neuron differentiation and provide an improved system for cell transplantation in a preclinical animal model of Parkinson's disease...

..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...

..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...

..These data suggest that MAP-1 mediates apoptosis through a mechanism that involves binding to Bax...

..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...

..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...

..Taken together, these findings support the notion that Bif-1 is an important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator, and loss of this proapoptotic molecule may contribute to tumorigenesis...

..These data thus show a functional incompatibility between hematopoietic and endodermal GATA factors in vivo and provide evidence indicating specific roles of the C-terminal region of GATA-1 in primitive erythropoiesis...

..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...

..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...

..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...

..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...

..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...

..These results indicate a predominant role of bcl-X(L) in preventing apoptosis in myeloma cells and suggest that the expression of bcl-2 or bcl-X(L) genes in B-cell tumors depends on the differentiation stage of the precursor normal cell...

..These findings point to a significant role for Bax and Bcl-xS in the regulation of apoptosis of secretory alveolar cells during involution...

..Thus, down-modulation of apoptosis selectively contributes to late steps in a tumorigenesis pathway...

..Our findings also suggest novel approaches to cancer therapy...

..Hence, Bim appears to act as a 'death ligand' which can only neutralize certain members of the pro-survival Bcl-2 sub-family...

..The findings reveal a hierarchy of functional interactions of BI-1 with Bcl-2/Bax family proteins in regulating ER Ca(2+) homeostasis...

..These results demonstrate how levels of BH3-only proteins, target affinity and the spectrum of neutralization of pro-survival proteins all contribute to killing activity...

..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...

..Our results suggest a way in which both Bim and Bax/Bak might be required for activated T cell apoptosis...

..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...

..We conclude that Bcl-xL is required for the development and function of CD4 Treg, which ameliorate lupus following treatment with a tolerogenic peptide...

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..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...

..In this study, we generated therapeutically active Tregs with an increased life span and hence greater therapeutic potential...

..These results indicate that the various functions of CD28 can be dissociated, and provide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28...

..Identification of Bcl-x gamma helps provide a molecular explanation of T cell activation and death after antigen engagement...

..This analysis also demonstrated that immunoglobulin gene rearrangement is less precise than previously appreciated...

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..e., BID and BAD) do not contribute to BAX-dependent cyt c release or apoptosis caused by TFD...

..To test the hypothesis that overexpression of genes coding for the anti-apoptotic proteins Bcl-2 or Bcl-XL in photoreceptor cells may prevent or delay photoreceptor degenerations...

..Furthermore, its distribution in multiple tissues of the embryo suggests that A1 plays a role in the regulation of physiological cell death during embryonic development...

..In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors...

..The findings of the present study provide insights into apoptotic mechanisms in mesothelioma cells and show similar patterns of gene expression to that reported in the human disease...

..Furthermore, our results link one of the immunodeficient traits caused by mutant Btk with the failure to properly regulate Bcl-xL...

..beta-Catenin/TCF is thus able to act as a signal to up-regulate Bcl-xL levels in DP thymocytes, resulting in their enhanced survival...

..In addition, myosin Va was identified as a novel Bcl-xL-interacting protein that might mediate the effects of Bcl-xL on tumor cell migration and invasion...

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..These proteins are suggested to interact with each other in the regulation of programmed cell death, apoptosis, but their specific role in growth control of uterine leiomyomas remains to be investigated...

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..This process of CD8(+) T cell activation, proliferation, and differentiation followed by rapid cell death may represent a novel mechanism of altered peptide ligand-induced apoptosis programmed by initial Ag receptor engagement...

..This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis...

..We investigated the importance of Bcl-xL for beta-cells by deleting the Bcl-x gene specifically in beta-cells and analyzing their survival in vivo and in culture...

..This survival pathway may contribute to the glial survival and activation seen in the spinal cord of ALS patients...

..Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS...

..In contrast, Bcl-xL overexpression can dramatically increase the malignant conversion rate of benign tumors, suggesting that inhibition of apoptosis can contribute to tumor progression...

..Signaling from toll-like receptors (TLRs) up-regulated Bcl-xL and improved DC survival. Our data suggest that differential expression of apoptosis signaling molecules regulates the lifespan of different DC subsets...

..Taken together, these findings demonstrate that although the terminal differentiation program is not altered by Bcl-x, acute stress responses within the skin can be influenced by regulators of apoptosis such as Bcl-x...

..Therefore, the genes regulating caspase-dependent cell death are expressed in embryonic organs in an E2F-independent manner and a developmental-related silencing event represses these genes in postmitotic adult tissues...

The bclx gene has been shown to regulate programmed cell death in vitro...

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..In summary, the expression profiles of Bcl-2 family members during liver regeneration suggest a cell-cycle-dependent regulation as well as a physiological role for these apoptosis-modulating genes during growth and proliferation...

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..The data suggest potential utility of c-Myb/p300 as a target for therapeutic intervention in thrombocytopenia of diverse origins...

..Our results also argue that the relative amounts of Bcl-2 and Bax are critical in regulating neuronal survival...

..These studies ascribe multifaceted functions specific to Erk2 in CD8 T cell activation, proliferation, and survival...

..In fact, HC11 cells unable to express bcl-X, die even in the presence of EGF. In this context, Bcl-XL emerges as a key anti-apoptotic molecule critical for mediating EGF cell survival...

..They also suggest that the Bcl-2 family of genes might be the only one capable of inhibiting apoptosis induced by multiple pathways without inducing cell proliferation...

..Moreover, the loop may have additional, as yet unknown, functions because it changes its shape when Bcl-xl binds Bim...

..We have therefore identified a powerful new BCL-X promoter and a novel exon that contributes to BCL-XL expression...

..Thus, Bcl-2 function is required for particular stages of fetal and postnatal myogenesis...

..We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis...

..In total, these results indicate a transition from Caspase-9- to Bax- and Bcl-X(L)-mediated neuronal apoptosis...

..This observation correlates with the induction of the bcl-X(L) mRNA, suggesting that P4 is one of the bcl-X promoters responsible for the generation of this antiapoptotic isoform...

..Bax activation at the mitochondrial membrane requires the generation of ROS and can be prevented by the overexpression of Bcl-XL...

..It would therefore be of interest to determine whether manipulation of respiratory chain function can be used to inhibit or enhance apoptosis in these conditions...

..However, the mechanisms by which statins induce apoptosis in tubular cells have not been fully addressed...

..The ability receptor-induced signals to regulate the splicing pattern of the complex Bcl-x gene may allow T-cells to respond appropriately to antigenic stimuli...

..Here we address whether Epo function during terminal maturation involves a cytokine-independent "default program," requiring only apoptosis inhibition through Epo-dependent upregulation of Bcl-X(L)...

..We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis...

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..The apoptotic activity of Blk is also inhibited by a dominant negative caspase-9, suggesting that Blk induces apoptosis through activation of the cytochrome c-Apaf-1-caspase-9 pathway...

..Accordingly, neurons from the deficient mice could not survive in culture even in the presence of neurotrophins. Our results suggest a cell-intrinsic role of Six1 and Six4 in the survival of early-generated trigeminal sensory neurons...

..Bcl-xL and p19 ARF loss together synergize to further accelerate Myc oncogenesis. Thus, differing lesions cooperate oncogenically with Myc by discrete mechanisms that can themselves synergize with each other...

..These results suggest that subchronic inhalation exposure to 1-BP vapor may affect the Bcl-xL expression in astrocytes...

..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...

The Bcl2-related genes, Bax and Bcl2l (formerly called Bclx), are involved in the regulation of apoptotic cell death, and the chromosome location of these two genes was determined in the mouse and rat by fluorescence in situ ..

..On the contrary, cells that overexpress Bcl-xL and Aiolos are unable to block apoptosis in the absence of IL-4. We propose a model for the regulation of the Bcl-xL anti-apoptotic role via Aiolos...

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..To observe the apoptotic characteristics of mouse spleen lymphocyte after lethal dose gamma-irradiation and its relationship to the expression of Bax and Bcl-XL proteins...

..Furthermore, they might reveal whether a combinatorial therapy of pan-ErbB tyrosine kinase inhibitors and Jak2 inhibitors would be beneficial for the treatment of ErbB2-positive breast cancers. ..

..The studies described in this proposal may lead to identification of a new therapeutic target in diabetes. ..

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..Furthermore, they might reveal whether a combinatorial therapy of pan-ErbB tyrosine kinase inhibitors and Jak2 inhibitors would be beneficial for the treatment of ErbB2-positive breast cancers. ..

..The genetic and molecular studies outlined in this application will help to predict the potential value of Tsg101 as a therapeutic target before a drug will be developed and tested in preclinical trials. ..

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..The studies described in this proposal may lead to identification of a new therapeutic target in diabetes. ..

..Ultimately, we aim to harness the fresh insights from these studies to generate prototype therapeutics that reactivate BAX-mediated apoptosis in human cancer. ..

..The genetic and molecular studies outlined in this application will help to predict the potential value of Tsg101 as a therapeutic target before a drug will be developed and tested in preclinical trials. ..

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..Walensky's development as an independent investigator at the interface of these notable fields. ..

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..The current proposal will dissect this pro-apoptotic cascade by identifying the precise downstream molecules that mediate the mitochondrial demise and detailing their mechanism of action. ..

..Danial's development as an independent investigator. Dr. Korsmeyer, a world leader in the fields of oncogenesis and apoptosis, has an excellent record of training and fostering independent investigators. ..

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