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Bcl2 Interacting Killer

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https://www.readbyqxmd.com/read/27906186/preimplantation-factor-is-an-anti-apoptotic-effector-in-human-trophoblasts-involving-p53-signaling-pathway
#1
Hadia Moindjie, Esther Dos Santos, Rita-Josiane Gouesse, Nelly Swierkowski-Blanchard, Valérie Serazin, Eytan R Barnea, François Vialard, Marie-Noëlle Dieudonné
From the earliest stages of gestation, embryonic-maternal interaction has a key role in a successful pregnancy. Various factors present during gestation may significantly influence this type of juxta/paracrine interaction. PreImplantation Factor (PIF) is a recently identified factor with activity at the fetomaternal interface. PIF is secreted by viable embryos and directly controls placental development by increasing the invasive capacity of human extravillous trophoblasts (EVTs). To further specify PIF's role in the human placenta, we analyzed the genome-wide expression profile of the EVT in the presence of a synthetic PIF analog (sPIF)...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27902785/apoptosis-related-gene-expression-profiling-in-hematopoietic-cell-fractions-of-mds-patients
#2
Saskia Mc Langemeijer, Niccolo Mariani, Ruth Knops, Christian Gilissen, Rob Woestenenk, Theo de Witte, Gerwin Huls, Bert A van der Reijden, Joop H Jansen
Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells...
2016: PloS One
https://www.readbyqxmd.com/read/27280444/hcv-mediated-apoptosis-of-hepatocytes-in-culture-and-viral-pathogenesis
#3
Erica Silberstein, Laura Ulitzky, Livia Alves Lima, Nicoleta Cehan, Andréa Teixeira-Carvalho, Philippe Roingeard, Deborah R Taylor
Chronic Hepatitis C Virus (HCV) infection is associated with progressive liver injury and subsequent development of fibrosis and cirrhosis. The death of hepatocytes results in the release of cytokines that induce inflammatory and fibrotic responses. The mechanism of liver damage is still under investigation but both apoptosis and immune-mediated processes may play roles. By observing the changes in gene expression patterns in HCV-infected cells, both markers and the causes of HCV-associated liver injury may be elucidated...
2016: PloS One
https://www.readbyqxmd.com/read/26662110/breast-cancer-cell-line-mda-mb-231-mirna-profile-expression-after-bik-interference-bik-involvement-in-autophagy
#4
Ruth Ruiz Esparza-Garrido, María Eugenia Torres-Márquez, Rubí Viedma-Rodríguez, Ana Claudia Velázquez-Wong, Fabio Salamanca-Gómez, Haydeé Rosas-Vargas, Miguel Ángel Velázquez-Flores
B-cell lymphoma 2 (BCL2)-interacting killer (apoptosis inducing) (BIK) has been proposed as a tumor suppressor in diverse types of cancers. However, BIK's overexpression in breast cancer (BC) and in non-small lung cancer cells (NSCLCs), associated with a poor prognosis, suggests its participation in tumor progression. In this study, we evaluated the global expression pattern of microRNAs (miRNAs), messenger RNA (mRNA) expression changes in autophagy, and autophagic flux after BIK interference. BIK gene expression was silenced by small interfering RNA (siRNA) in BC cell MDA-MB-231, and BIK interference efficiency was tested by real-time PCR and by Western blotting...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26253785/bnip3-and-bnip3l-mediated-mitophagy-promotes-the-generation-of-natural-killer-cell-memory
#5
Timothy E O'Sullivan, Lexus R Johnson, Helen H Kang, Joseph C Sun
Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as clonal expansion, contraction, and generation of long-lived "memory" cells, processes poorly understood at the molecular level. Here, we found that as proliferating NK cells accumulated dysfunctional mitochondria during viral infection, a protective mitophagy pathway was induced during the contraction phase to promote their survival in a reactive oxygen species (ROS)-dependent manner. Inhibition of mechanistic target of rapamycin (mTOR) or activation of AMP-activated protein kinase (AMPK) during the contraction-to-memory phase transition of the antiviral response increased autophagic activity and enhanced memory NK cell numbers through an Atg3-dependent mechanism...
August 18, 2015: Immunity
https://www.readbyqxmd.com/read/26179084/the-roles-of-the-interaction-of-bcl2-antagonist-killer-1-apoptotic-peptidase-activating-factor-1-and-selenium-in-the-pathogenesis-of-kashin-beck-disease
#6
Sen Wang, Chen Duan, Feng Zhang, Xi Wang, Xiong Guo
BCL2-antagonist/killer 1 (BAK1) and apoptotic peptidase activating factor 1 (APAF1) are significant genes in apoptosis signalling pathway of Kashin-Beck disease (KBD). We aimed to verify the protein expression levels of BAK1 and APAF1 in the cartilage and chondrocytes of patients with KBD. Additionally, we explored the relationship between the levels of these proteins and selenium concentration. Chondrocytes was cultured and treated with sodium selenite in vitro. Immunohistochemistry and Western blotting were used to verify the expression levels of BAK1 and APAF1...
March 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/25767602/induction-of-bcl2-interacting-killer-bik-is-mediated-for-anti-cancer-activity-of-curcumin-in-human-head-and-neck-squamous-cell-carcinoma-cells
#7
Yue Xi, Hang Gao, Michael U Callaghan, Andrew M Fribley, Danielle M Garshott, Zhi-Xiang Xu, Qinghua Zeng, Yu-Lin Li
Naturally occurring diarylheptanoid curcumin (CUR), a principal component of the Asian spice turmeric, has been shown to have anti-cancer effects in many tumor types. However, a detailed mechanism regarding CUR induced tumor cell killing remain to be comprehensively explored. Using two head neck squamous cell carcinoma (HNSCC) cell lines FaDu (hypopharyngeal) and Cal27 (tongue), we demonstrated a novel mechanism by which CUR levies the cytotoxic effect. We found that CUR induced upregulation of pro-apoptotic Bik, down-regulation of survival signaling by AKT and NF-κB prior to the induction of the caspase-cascade reduction of cell proliferation, are primary mechanisms of CUR-induced cell death, thus providing insights into the anti-tumor activity of CUR in HNSCC cells...
2015: Journal of Cancer
https://www.readbyqxmd.com/read/25436775/induced-autoimmunity-against-gonadal-proteins-affects-gonadal-development-in-juvenile-zebrafish
#8
Christopher Presslauer, Kazue Nagasawa, Dalia Dahle, Joanna Babiak, Jorge M O Fernandes, Igor Babiak
A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development...
2014: PloS One
https://www.readbyqxmd.com/read/25275009/activation-of-mitochondrial-protease-oma1-by-bax-and-bak-promotes-cytochrome-c-release-during-apoptosis
#9
Xian Jiang, Hui Jiang, Zhirong Shen, Xiaodong Wang
Intrinsic apoptotic stimuli initiate mammalian cells' apoptotic program by first activating the proteins that have only Bcl-2 homology domain 3 (BH3), such as Bcl-2 interacting mediator of cell death (Bim) and truncated BH3 interacting death domain agonist (tBid), which in turn trigger conformational changes in BCL2-associated X (Bax) and BCL2-antagonist/killer (Bak) proteins that enable oligomer formation on the mitochondria, causing cytochrome c and other apoptogenic proteins in the intermembrane space to leak out...
October 14, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25165875/combination-of-lenalidomide-with-vitamin-d3-induces-apoptosis-in-mantle-cell-lymphoma-via-demethylation-of-bik
#10
C Brosseau, C Dousset, C Touzeau, S Maïga, P Moreau, M Amiot, S Le Gouill, C Pellat-Deceunynck
Mantle cell lymphoma (MCL) is a currently incurable B-cell malignancy. Lenalidomide (Len) has been demonstrated to be one of the most efficient new treatment options. Because Len and 1α,25-dihydroxyvitamin (VD3) synergize to kill breast cancer cells, we investigated whether VD3 could increase the ability of Len to induce MCL cell death. While MCL cells were weakly sensitive to Len (1 μM), the addition of VD3 at physiological dose (100 nM) strongly increased cell death, accompanied by slowdown in cell cycle progression in MCL cell lines (n=4 out of 6) and primary samples (n=5 out of 7)...
2014: Cell Death & Disease
https://www.readbyqxmd.com/read/24788683/increase-of-zinc-finger-protein-179-in-response-to-ccaat-enhancer-binding-protein-delta-conferring-an-antiapoptotic-effect-in-astrocytes-of-alzheimer-s-disease
#11
Shao-Ming Wang, Yi-Chao Lee, Chiung-Yuan Ko, Ming-Derg Lai, Ding-Yen Lin, Ping-Chieh Pao, Jhih-Ying Chi, Yu-Wei Hsiao, Tsung-Lin Liu, Ju-Ming Wang
Reactive astrogliosis is a cellular manifestation of neuroinflammation and occurs in response to all forms and severities of the central nervous system (CNS)'s injury and disease. Both astroglial proliferation and antiapoptotic processes are aspects of astrogliosis. However, the underlying mechanism of this response remains poorly understood. In addition, little is known about why activated astrocytes are more resistant to stress and inflammation. CCAAT/enhancer binding protein delta (CEBPD) is a transcription factor found in activated astrocytes that surround β-amyloid plaques...
February 2015: Molecular Neurobiology
https://www.readbyqxmd.com/read/24527759/the-increase-in-bik-expression-following-erk1-2-pathway-inhibition-is-a-consequence-of-g%C3%A2-cell-cycle-arrest-and-not-a-direct-effect-on-bik-protein-stability
#12
COMPARATIVE STUDY
Matthew J Sale, Simon J Cook
BIK (BCL2-interacting killer) is a pro-apoptotic BH3 (BCL2 homology domain 3)-only protein and a member of the BCL2 protein family. It was proposed recently that BIK abundance is controlled by ERK1/2 (extracellular-signal-regulated kinase 1/2)-catalysed phosphorylation, which targets the protein for proteasome-dependent destruction. In the present study, we examined ERK1/2-dependent regulation of BIK, drawing comparisons with BIM(EL) (BCL2-interacting mediator of cell death; extra long), a well-known target of ERK1/2...
May 1, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/24305946/bag-6-a-jack-of-all-trades-in-health-and-disease
#13
REVIEW
Janina Binici, Joachim Koch
BCL2-associated athanogene 6 (BAG-6) (also Bat-3/Scythe) was discovered as a gene product of the major histocompatibility complex class III locus. The Xenopus ortholog Scythe was first identified to act as an anti-apoptotic protein. Subsequent studies unraveled that the large BAG-6 protein contributes to a number of cellular processes, including apoptosis, gene regulation, protein synthesis, protein quality control, and protein degradation. In this context, BAG-6 acts as a multifunctional chaperone, which interacts with its target proteins for shuttling to distinct destinations...
May 2014: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/24229683/a-preliminary-study-of-genes-related-to-concomitant-chemoradiotherapy-resistance-in-advanced-uterine-cervical-squamous-cell-carcinoma
#14
Ju-Sheng An, Man-Ni Huang, Yong-Mei Song, Nan Li, Ling-Ying Wu, Qi-Min Zhan
BACKGROUND: Tumor intrinsic chemoradiotherapy resistance is the primary factor in concomitant chemoradiotherapy failure in advanced uterine cervical squamous cell carcinoma. This study aims to identify a set of genes and molecular pathways related to this condition. METHODS: Forty patients with uterine cervical squamous cell carcinoma in International Federation of Gynecology and Obstetrics stage IIb or IIIb, treated with platinum-based concomitant chemoradiotherapy between May 2007 and December 2012, were enrolled in this trial...
November 2013: Chinese Medical Journal
https://www.readbyqxmd.com/read/24133212/a-soluble-fragment-of-the-tumor-antigen-bcl2-associated-athanogene-6-bag-6-is-essential-and-sufficient-for-inhibition-of-nkp30-receptor-dependent-cytotoxicity-of-natural-killer-cells
#15
Janina Binici, Jessica Hartmann, Julia Herrmann, Christine Schreiber, Steffen Beyer, Günnur Güler, Vitali Vogel, Franz Tumulka, Rupert Abele, Werner Mäntele, Joachim Koch
Immunosurveillance of tumor cells depends on NKp30, a major activating receptor of human natural killer (NK) cells. The human BCL2-associated athanogene 6 (BAG-6, also known as BAT3; 1126 amino acids) is a cellular ligand of NKp30. To date, little is known about the molecular details of this receptor ligand system. Within the current study, we have located the binding site of NKp30 to a sequence stretch of 250 amino acids in the C-terminal region of BAG-6 (BAG-6(686-936)). BAG-6(686-936) forms a noncovalent dimer of 57-59 kDa, which is sufficient for high affinity interaction with NKp30 (KD < 100 nM)...
November 29, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24116174/dynamics-of-bcl-xl-in-water-and-membrane-molecular-simulations
#16
Atanu Maity, Seema Yadav, Chandra S Verma, Shubhra Ghosh Dastidar
The Bcl2 family of proteins is capable of switching the apoptotic machinery by directly controlling the release of apoptotic factors from the mitochondrial outer membrane. They have 'pro' and 'anti'-apoptotic subgroups of proteins which antagonize each other's function; however a detailed atomistic understanding of their mechanisms based on the dynamical events, particularly in the membrane, is lacking. Using molecular dynamics simulations totaling 1.6µs we outline the major differences between the conformational dynamics in water and in membrane...
2013: PloS One
https://www.readbyqxmd.com/read/23824742/novel-small-molecule-inhibitors-of-bcl-xl-to-treat-lung-cancer
#17
Dongkyoo Park, Andrew T Magis, Rui Li, Taofeek K Owonikoko, Gabriel L Sica, Shi-Yong Sun, Suresh S Ramalingam, Fadlo R Khuri, Walter J Curran, Xingming Deng
Bcl-XL is a major antiapoptotic protein in the Bcl-2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl-2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. Here, we screened small molecules that selectively target the BH3 domain (aa 90-98) binding pocket of Bcl-XL using the UCSF DOCK 6.1 program suite and the NCI chemical library database. We identified two new Bcl-XL inhibitors (BXI-61 and BXI-72) that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells...
September 1, 2013: Cancer Research
https://www.readbyqxmd.com/read/23589839/myc-induced-ampk-phospho-p53-pathway-activates-bak-to-sensitize-mitochondrial-apoptosis
#18
Anni I Nieminen, Vilja M Eskelinen, Heidi M Haikala, Topi A Tervonen, Yan Yan, Johanna I Partanen, Juha Klefström
Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Here, we show that Myc-induced altered glutamine metabolism involves ATP depletion and activation of the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15...
May 14, 2013: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/23519116/a-myosin-va-tail-fragment-sequesters-dynein-light-chains-leading-to-apoptosis-in-melanoma-cells
#19
T C Izidoro-Toledo, A C Borges, D D Araújo, D P S Leitão Mazzi, F O Nascimento Júnior, J F Sousa, C P Alves, A P B Paiva, D M Trindade, E V Patussi, P M Peixoto, K W Kinnally, E M Espreafico
Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that overexpression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis...
March 21, 2013: Cell Death & Disease
https://www.readbyqxmd.com/read/23329644/systems-analysis-of-bcl2-protein-family-interactions-establishes-a-model-to-predict-responses-to-chemotherapy
#20
Andreas U Lindner, Caoimhín G Concannon, Gerhardt J Boukes, Mary D Cannon, Fabien Llambi, Deborah Ryan, Karen Boland, Joan Kehoe, Deborah A McNamara, Frank Murray, Elaine W Kay, Suzanne Hector, Douglas R Green, Heinrich J Huber, Jochen H M Prehn
Apoptotic desensitization is a hallmark of cancer cells, but present knowledge of molecular systems controlling apoptosis has yet to provide significant prognostic insights. Here, we report findings from a systems study of the intrinsic pathway of apoptosis by BCL2 family proteins and clinical translation of its findings into a model with applications in colorectal cancer (CRC). By determining absolute protein quantifications in CRC cells and patient tumor samples, we found that BAK and BAX were expressed more highly than their antiapoptotic inhibitors...
January 15, 2013: Cancer Research
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