Genomes and Genes
bcl x protein
Summary: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS and is a regulatory subunit for PROTEIN PHOSPHATASE 1. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
- Vassallo R, Walters P, Lamont J, Kottom T, Yi E, Limper A. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study. Respir Res. 2010;11:45 pubmed publisher..Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD...
- Bouaziz C, Martel C, Sharaf el Dein O, Abid Essefi S, Brenner C, Lemaire C, et al. Fusarial toxin-induced toxicity in cultured cells and in isolated mitochondria involves PTPC-dependent activation of the mitochondrial pathway of apoptosis. Toxicol Sci. 2009;110:363-75 pubmed publisher..Taken together, these data indicate that mitochondria play a pivotal role in both ZEN- and T-2 toxin-induced apoptosis and that PTPC members and proteins of Bcl-2 family should be interesting targets to overcome fusarotoxin toxicity...
- Shroff E, Snyder C, Budinger G, Jain M, Chew T, Khuon S, et al. BH3 peptides induce mitochondrial fission and cell death independent of BAX/BAK. PLoS ONE. 2009;4:e5646 pubmed publisher..These results suggest that pro-survival BCL-2 proteins regulate mitochondrial fission and cell death in the absence of BAX and BAK. ..
- Arakawa Y, Saito S, Yamada H, Aiba K. Simultaneous treatment with camptothecin and valproic acid suppresses induction of Bcl-X(L) and promotes apoptosis of MCF-7 breast cancer cells. Apoptosis. 2009;14:1076-85 pubmed publisher..Taken together, our results suggest that simultaneous administration of camptothecin and valproic acid might be useful for anticancer therapy. ..
- Matsumura N, Tsuji T, Sumida T, Kokubo M, Onimaru M, Doi N, et al. mRNA display selection of a high-affinity, Bcl-X(L)-specific binding peptide. FASEB J. 2010;24:2201-10 pubmed publisher..We suggest that mRNA display is a powerful technique to identify peptide inhibitors with high affinity and specificity for disease-related proteins. ..
- Yang Y, Huang F, Ren Y, Xing L, Wu Y, Li Z, et al. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice. Oncol Res. 2009;18:1-8 pubmed..SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer...
- Zhang H, Li M, Han Y, Hong L, Gong T, Sun L, et al. Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci. 2010;55:2545-51 pubmed publisher..MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer. ..
- Li H, Li C. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein. J Comput Chem. 2010;31:2014-22 pubmed publisher..These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively. ..
- Brignatz C, Paronetto M, Opi S, Cappellari M, Audebert S, Feuillet V, et al. Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn. Mol Cell Biol. 2009;29:6438-48 pubmed publisher..Our results illustrate a novel mechanism of evolution that may contribute to the complexity of Src kinase regulation. ..
- Dahlmann Noor A, Vijay S, Limb G, Khaw P. Strategies for optic nerve rescue and regeneration in glaucoma and other optic neuropathies. Drug Discov Today. 2010;15:287-99 pubmed publisher..Increasing understanding of the pathways involved in directed axon growth and manipulation of stem and progenitor cells towards an RGC fate have facilitated first successes in animal models of glaucoma. ..
- Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, et al. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest. 2009;119:2399-411 pubmed publisher..Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis. ..
- Yuan J, Crittenden R, Bender T. c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL. J Immunol. 2010;184:2793-804 pubmed publisher..Thus, Bcl-xL is a novel mediator of c-Myb activity during normal T cell development. ..
- Han J, Goldstein L, Hou W, Gastman B, Rabinowich H. Regulation of mitochondrial apoptotic events by p53-mediated disruption of complexes between antiapoptotic Bcl-2 members and Bim. J Biol Chem. 2010;285:22473-83 pubmed publisher..We propose that mitochondrial p53 functions as a Bim derepressor by releasing Bim from sequestrating complexes with Mcl-1, Bcl-2, and Bcl-XL, and allowing its engagement in Bak/Bax activation. ..
- Mattioli B, Giordani L, Quaranta M, Viora M. Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3K-Akt signaling pathway. FEBS Lett. 2009;583:1102-6 pubmed publisher..These results provide insights on the immunoregulatory function of leptin, supporting a potential application in immunotherapeutic approaches. ..
- Hilton D, Kile B, Alexander W. Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia. Blood. 2009;113:5599-604 pubmed publisher..The data suggest potential utility of c-Myb/p300 as a target for therapeutic intervention in thrombocytopenia of diverse origins. ..
- Ryu K, Susa M, Choy E, Yang C, Hornicek F, Mankin H, et al. Oleanane triterpenoid CDDO-Me induces apoptosis in multidrug resistant osteosarcoma cells through inhibition of Stat3 pathway. BMC Cancer. 2010;10:187 pubmed publisher..This study provides the framework for the clinical evaluation of CDDO-Me, either as monotherapy or perhaps even more effectively in combination with doxorubicin to treat osteosarcoma and overcome drug resistance. ..
- Lim D, Park J. Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1060-8 pubmed publisher..The induction of p53 results in the translocation of Bax to the mitochondria, which contributes to fisetin-induced apoptosis in HCT-116 cells. ..
- Jin X, Qiu L, Zhang D, Zhang M, Wang Z, Guo Z, et al. Chemosensitization in non-small cell lung cancer cells by IKK inhibitor occurs via NF-kappaB and mitochondrial cytochrome c cascade. J Cell Mol Med. 2009;13:4596-607 pubmed publisher..These data strengthen the rationale for using parthenolide to decrease the apoptotic threshold via caspase-dependent processes for treatment of non-small cell lung cancer with paclitaxel chemoresistance. ..
- Elayat G, Selim A, Wells C. Cell turnover in apocrine metaplasia and apocrine adenosis of the breast. Ann Diagn Pathol. 2010;14:1-7 pubmed publisher..Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions. ..
- Russell D, Ross H, Lane E. ERK involvement in resistance to apoptosis in keratinocytes with mutant keratin. J Invest Dermatol. 2010;130:671-81 pubmed publisher..The consequences of constitutive expression of large amounts of defective structural protein in a tissue cell must be properly understood for the development of safe and effective therapies for these disorders. ..
- Schulz R, Vogel T, Mashima T, Tsuruo T, Krieglstein K. Involvement of Fractin in TGF-beta-induced apoptosis in oligodendroglial progenitor cells. Glia. 2009;57:1619-29 pubmed publisher..In conclusion, we show that Fractin is not only an apoptotic marker, but has indeed a functional role in apoptotic signaling in oligodendrocytes. ..
- Zhong X, Matsushita M, Plotkin J, Riviere I, Sadelain M. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. Mol Ther. 2010;18:413-20 pubmed publisher..These findings further support the concept of integrating optimized costimulatory properties into recombinant antigen receptors to augment the survival and function of genetically targeted T cells within the tumor microenvironment. ..
- Peng J, Lapolla S, Zhang Z, Lin J. The cytosolic domain of Bcl-2 forms small pores in model mitochondrial outer membrane after acidic pH-induced membrane association. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009;26:130-7 pubmed..Therefore, Bcl-2 and Bax may form different size pores in MOM, and while the large pore formed by Bax may release cytochrome c during apoptosis, the small pore formed by Bcl-2 may maintain the normal MOM permeability. ..
- Wang Y, Niu X, Qu Y, Wu J, Zhu Y, Sun W, et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett. 2010;295:110-23 pubmed publisher..Therefore, modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant ovarian cancer. ..
- Cao X, Wang A, Wang C, Mao D, Lu M, Cui Y, et al. Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway. Chem Biol Interact. 2010;183:357-62 pubmed publisher..Taken together, these findings suggest that the surfactin induces apoptosis through a ROS/JNK-mediated mitochondrial/caspase pathway. ..
- Peng C, Guo W, Ji T, Ren T, Yang Y, Li D, et al. Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway. Cancer Biol Ther. 2009;8:1729-36 pubmed..In conclusion, our findings demonstrate that sorafenib is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that sorafenib may be a new therapeutic option for patients with synovial sarcoma...
- Son Y, Lee J, Hitron J, Pan J, Zhang Z, Shi X. Cadmium induces intracellular Ca2+- and H2O2-dependent apoptosis through JNK- and p53-mediated pathways in skin epidermal cell line. Toxicol Sci. 2010;113:127-37 pubmed publisher..These results suggest that cadmium induces apoptosis via the activation of JNK- and p53-mediated signaling, where calcium ion and hydrogen peroxide act as the pivotal mediators of the apoptotic signaling. ..
- Kwakkenbos M, DIEHL S, Yasuda E, Bakker A, Van Geelen C, Lukens M, et al. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med. 2010;16:123-8 pubmed publisher..This method provides a new tool to study B cell biology and signal transduction through antigen-specific B cell receptors and for the rapid generation of high-affinity human monoclonal antibodies. ..
- Cao Y, Li H, Liu H, Zheng C, Ji H, Liu X. The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression. Cell Res. 2010;20:99-108 pubmed publisher..These findings identify LKB1 as a critical factor for the survival of DP thymocytes through regulation of AMPK activation and Bcl-XL expression. ..
- Sasazawa Y, Futamura Y, Tashiro E, Imoto M. Vacuolar H+-ATPase inhibitors overcome Bcl-xL-mediated chemoresistance through restoration of a caspase-independent apoptotic pathway. Cancer Sci. 2009;100:1460-7 pubmed publisher..V-ATPase inhibition will be a promising therapeutic approach for Bcl-2- or Bcl-xL-overexpressing malignancies. ..
- Kim T, Kim Y, Shin S, Kim C, Yu I, Kim S. Synergistic hepatotoxicity of N,N-dimethylformamide with carbon tetrachloride in association with endoplasmic reticulum stress. Chem Biol Interact. 2010;184:492-501 pubmed publisher..Our results demonstrate that DMF treatment in combination with CCl(4) synergistically increases hepatocyte death, which may be associated with the induction of severe ER stress. ..
- Lieber J, Kirchner B, Eicher C, Warmann S, Seitz G, Fuchs J, et al. Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma cells. Pediatr Blood Cancer. 2010;55:1089-95 pubmed publisher..In Hepatoblastoma (HB) apoptosis regulation contributes to resistance and therapy failure, therefore we modulated apoptosis sensitivity of HB cells for an improved cytotoxic activity of commonly used drugs...
- Goel G, Guo M, Ding J, Dornbos D, Ali A, Shenaq M, et al. Combined effect of tumor necrosis factor (TNF)-alpha and heat shock protein (HSP)-70 in reducing apoptotic injury in hypoxia: a cell culture study. Neurosci Lett. 2010;483:162-6 pubmed publisher..This study suggested that TNF-alpha and HSP-70 together enhance the decrease in pro-apoptotic protein levels and the increase in anti-apoptotic protein levels in the event of neuronal hypoxia through ERK1/2 signal transduction. ..
- Chen F, Xu Y, Luo Y, Zheng D, Song Y, Yu K, et al. Down-regulation of Stat3 decreases invasion activity and induces apoptosis of human glioma cells. J Mol Neurosci. 2010;40:353-9 pubmed publisher..In addition, down-regulation of Stat3 can suppress the expression of MMP-2, Bcl-xL and survivin but not 67LR. These results further indicate that Stat3 plays a key role in the invasion and apoptosis of human glioma cell line U251. ..
- Tang C, Xue H, Huang H, Wang X. Tanshinone IIA inhibits constitutive STAT3 activation, suppresses proliferation, and induces apoptosis in rat C6 glioma cells. Neurosci Lett. 2010;470:126-9 pubmed publisher..These results suggest that Tan IIA may serve as an effective adjunctive reagent in the treatment of glioma for its targeting of constitutive STAT3 signaling. ..
- Ma X, Zhao Y, Li Y, Lu H, He Y. Relevance of Bcl-x expression in different types of endometrial tissues. J Exp Clin Cancer Res. 2010;29:14 pubmed publisher..76). The abnormal expressions of Bcl-xs and Bcl-xl were one of the molecular mechanisms for the pathogenesis of endometrial carcinoma, and altered ratio between these two might involve in the onset of endometrial carcinoma. ..
- Brotin E, Meryet Figuière M, Simonin K, Duval R, Villedieu M, Leroy Dudal J, et al. Bcl-XL and MCL-1 constitute pertinent targets in ovarian carcinoma and their concomitant inhibition is sufficient to induce apoptosis. Int J Cancer. 2010;126:885-95 pubmed publisher..Therefore, Bcl-X(L) and MCL-1 targeted strategies could constitute an efficient therapeutic tool for the treatment of chemoresistant ovarian carcinoma, in association with conventional chemotherapy. ..
- Sykes S, Stanek T, Frank A, Murphy M, McMahon S. Acetylation of the DNA binding domain regulates transcription-independent apoptosis by p53. J Biol Chem. 2009;284:20197-205 pubmed publisher..These data support a model whereby Lys-120 acetylation contributes to both the transcription-dependent and -independent apoptotic pathways induced by p53. ..
- Chung H, Lee H, Lamoke F, Hrushesky W, Wood P, Jahng W. Neuroprotective role of erythropoietin by antiapoptosis in the retina. J Neurosci Res. 2009;87:2365-74 pubmed publisher..Together, these data support the premise that EPO and its EPOR interactions represent an important retinal shield from physiologic and pathologic light-induced oxidative injury. ..
- Yoo K, Yim H, Jang G, Bae I, Choi B, Hong Y, et al. Endothelin A receptor blockade influences apoptosis and cellular proliferation in the developing rat kidney. J Korean Med Sci. 2009;24:138-45 pubmed publisher..In conclusion, inhibition of endogenous endothelins impairs renal growth, in which decreased cellular proliferation, increased apoptosis and decreased expressions of renal Bcl-X(L) and Bax are possibly implicated. ..
- Chetoui N, Boisvert M, Gendron S, Aoudjit F. Interleukin-7 promotes the survival of human CD4+ effector/memory T cells by up-regulating Bcl-2 proteins and activating the JAK/STAT signalling pathway. Immunology. 2010;130:418-26 pubmed publisher..A further understanding of the mechanisms of IL-7 signalling in effector/memory T cells associated with autoimmune inflammatory diseases may lead to potential new therapeutic avenues. ..
- Soltani Arabshahi R, Leboeuf C, Rivet J, Pisonero H, Zhao W, Bachelez H, et al. Bcl-xL gene expression correlated with lower apoptotic cell numbers and shorter progression-free survival in PCFCL. J Invest Dermatol. 2009;129:1703-9 pubmed publisher..Moreover, the inverse correlation between bcl-xL expression levels and apoptotic cell numbers suggests that bcl-xL, through its antiapoptotic effect, might contribute to tumor cell survival in PCFCL. ..
- Hikita H, Takehara T, Kodama T, Shimizu S, Hosui A, Miyagi T, et al. BH3-only protein bid participates in the Bcl-2 network in healthy liver cells. Hepatology. 2009;50:1972-80 pubmed publisher..Healthy liver cells are addicted to a single Bcl-2-like molecule because of BH3 stresses, and therefore special caution may be required for the use of the Bcl-2 inhibitor for cancer therapy. ..
- Chen Q, Davidson T, Huter E, Shevach E. Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival. J Immunol. 2009;183:4458-66 pubmed publisher..Development of methods to selectively stimulate TLR2 on Treg may lead to a novel approaches for the treatment of autoimmune diseases. ..
- Rossi M, Bang J, Mazur S, Iera J, Phillips D, Zambetti G, et al. Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L). Bioorg Med Chem Lett. 2009;19:2429-34 pubmed publisher..These findings highlight a novel approach to the development of small molecules that promote apoptosis. ..
- Yang L, Wang L, Zhao C, Zhu X, Hou Y, Jun P, et al. Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood. 2010;116:4307-16 pubmed publisher..The abnormal expression of sTRAIL in plasma and TRAIL and Bcl-xL in megakaryocytes may play a role in the pathogenesis of impaired megakaryocyte apoptosis in ITP. ..
- Brutus N, Hanley S, Ashraf Q, Mishra O, Delivoria Papadopoulos M. Effect of hyperoxia on serine phosphorylation of apoptotic proteins in mitochondrial membranes of the cerebral cortex of newborn piglets. Neurochem Res. 2009;34:1219-25 pubmed publisher..We speculate that phosphorylation of Bcl-2 and Bcl-xl will result in loss of their anti-apoptotic potential by preventing their dimerization with Bax leading to activation of the caspase cascade of neuronal death. ..
- Kurita Ochiai T, Ochiai K. Butyric acid induces apoptosis via oxidative stress in Jurkat T-cells. J Dent Res. 2010;89:689-94 pubmed publisher..These results suggest that butyric acid is involved in mitochondrial-dysfunction- and endoplasmic reticulum stress-mediated apoptosis in human Jurkat T-cells via a ROS-dependent mechanism...