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Bcl2 Interacting Killer

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https://www.readbyqxmd.com/read/28986568/bik-reduces-hyperplastic-cells-by-increasing-bak-and-activating-dapk1-to-juxtapose-er-and-mitochondria
#1
Yohannes A Mebratu, Ivan Leyva-Baca, Marc G Wathelet, Neal Lacey, Hitendra S Chand, Augustine M K Choi, Yohannes Tesfaigzi
Bik reduces hyperplastic epithelial cells by releasing calcium from endoplasmic reticulum stores and causing apoptosis, but the detailed mechanisms are not known. Here we report that Bik dissociates the Bak/Bcl-2 complex to enrich for ER-associated Bak and interacts with the kinase domain of DAPk1 to form Bik-DAPk1-ERK1/2-Bak complex. Bik also disrupts the Bcl2-IP3R interaction to cause ER Ca(2+) release. The ER-associated Bak interacts with the kinase and calmodulin domains of DAPk1 to increase the contact sites of ER and mitochondria, and facilitate ER Ca(2+) uptake by mitochondria...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28769046/kaiso-protects-human-umbilical-vein-endothelial-cells-against-apoptosis-by-differentially-regulating-the-expression-of-b-cell-cll-lymphoma-2-family-members
#2
Xiaodong Xue, Jian Zhang, Huai Lan, Yinli Xu, Huishan Wang
Endothelial cell injury can promote the development of various cardiovascular diseases, thus, fully understanding the mechanisms underlying the maintenance of vascular endothelial cell homoeostasis may help prevent and treat cardiovascular disease. Kaiso, a zinc finger and BTB domain containing transcription factor, is key to embryonic development and cancer, but how Kaiso interacts with vascular endothelium is not fully understood. We report that Kaiso has an anti-apoptotic function in human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMEC-1s)...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720543/bik-is-involved-in-braf-mek-inhibitor-induced-apoptosis-in-melanoma-cell-lines
#3
Andreas Borst, Sebastian Haferkamp, Johannes Grimm, Manuel Rösch, Guannan Zhu, Sen Guo, Chunying Li, Tianwen Gao, Svenja Meierjohann, David Schrama, Roland Houben
In patients with BRAF-mutated melanoma specific inhibitors of BRAF(V600E) and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAF(V600E)-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells)...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28151486/star-pap-a-poly-a-polymerase-functions-as-a-tumor-suppressor-in-an-orthotopic-human-breast-cancer-model
#4
C Yu, Y Gong, H Zhou, M Wang, L Kong, J Liu, T An, H Zhu, Y Li
Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/27906186/preimplantation-factor-is-an-anti-apoptotic-effector-in-human-trophoblasts-involving-p53-signaling-pathway
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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