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Bcl interacting killer

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https://www.readbyqxmd.com/read/29566767/methotrexate-upregulates-circadian-transcriptional-factors-par-bzip-to-induce-apoptosis-on-rheumatoid-arthritis-synovial-fibroblasts
#1
Kohjin Suzuki, Kohsuke Yoshida, Takeshi Ueha, Kenta Kaneshiro, Ayako Nakai, Naonori Hashimoto, Koto Uchida, Teppei Hashimoto, Yoshiko Kawasaki, Nao Shibanuma, Natsuko Nakagawa, Yoshitada Sakai, Akira Hashiramoto
BACKGROUND: Effects of methotrexate (MTX) on the proliferation of rheumatoid arthritis (RA) synovial fibroblasts are incompletely understood. We explored actions of MTX in view of circadian transcriptions of synovial fibroblasts. METHODS: Under treatment with MTX, expression of core circadian clock genes, circadian transcriptional factor proline and acidic amino acid-rich basic leucine zipper (PAR bZIP), and proapoptotic molecule Bcl-2 interacting killer (Bik) was examined by real-time polymerase chain reaction...
March 22, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29375685/bnip3-bcl-2-mediated-apoptosis-induced-by-cyclic-tensile-stretch-in-human-cartilage-endplate-derived-stem-cells
#2
Chao Yuan, Luqiao Pu, Zhiliang He, Jian Wang
The present study aimed to investigate the molecular mechanisms of cyclic stretch-induced apoptosis in human intervertebral disc cartilage endplate-derived stem cells (CESCs). CESCs were stretched by the Flexercell-4000™ Tension Plus system, the effect on cell viability was measured by a Cell Counting Kit-8 assay, while cell apoptosis was detected by flow cytometry. Western blot analysis was used to evaluate the expression of B-cell lymphoma 2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), Bcl-2, Bcl-2 homologous antagonist killer (Bak), Bcl-2-associated X protein (Bax), Bcl extra large (Bcl-xl) and the activity of caspase-3, while Z-VAD-FMK was used to inhibit caspase-3...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29374142/the-bax-bak-like-protein-bok-is-a-prognostic-marker-in-colorectal-cancer
#3
Steven Carberry, Beatrice D'Orsi, Naser Monsefi, Manuela Salvucci, Orna Bacon, Joanna Fay, Markus Rehm, Deborah McNamara, Elaine W Kay, Jochen M H Prehn
The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members of the BCL-2 protein family. Activation of this death pathway plays a crucial role in cancer progression and chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that stage II and III colorectal cancer patients possessed decreased levels of BOK protein in their tumours compared to matched normal tissue...
January 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29344198/combination-of-cecropinxj-and-ly294002-induces-synergistic-cytotoxicity-and-apoptosis-in-human-gastric-cancer-cells-via-inhibition-of-the-pi3k-akt-signaling-pathway
#4
Li-Jie Xia, Yan-Ling Wu, Fu-Chun Zhang
The aim of the present study was to investigate the cytotoxic and apoptotic effects of cecropinXJ against human gastric cancer BGC823 cells, either alone, or in combination with a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. Cell viability and the apoptosis rate were measured using flow cytometry with Annexin-V staining. Additionally, the expression levels of several RAC-α serine/threonine kinase (Akt) phosphorylation-associated proteins and apoptosis-regulating proteins were evaluated by western blot analysis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#5
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29156771/novel-post-transcriptional-and-post-translational-regulation-of-pro-apoptotic-protein-bok-and-anti-apoptotic-protein-mcl-1-determine-the-fate-of-breast-cancer-cells-to-survive-or-die
#6
Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Subapriya Rajamanickam, Santosh Timilsina, Rosa Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, Ratna K Vadlamudi, Manjeet K Rao
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050237/modulation-of-the-nur77-bcl-2-apoptotic-pathway-by-p38%C3%AE-mapk
#7
Jie Liu, Guang-Hui Wang, Ying-Hui Duan, Yi Dai, Yuzhou Bao, Mengjie Hu, Yu-Qi Zhou, Mingyu Li, Fuquan Jiang, Hu Zhou, Xin-Sheng Yao, Xiao-Kun Zhang
Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2 pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2 pathway by CCE9 was associated with its activation of p38α MAPK...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29033852/activation-of-casein-kinase-ii-by-gallic-acid-induces-bik-bax-bak-mediated-er-ca-ros-dependent-apoptosis-of-human-oral-cancer-cells
#8
Meng-Liang Lin, Shih-Shun Chen
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca++ )-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca++ release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca+ + and ROS, cytochrome c (Cyt c ) release from the mitochondria, Ψm loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28986568/bik-reduces-hyperplastic-cells-by-increasing-bak-and-activating-dapk1-to-juxtapose-er-and-mitochondria
#9
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-IP3 R interaction to cause ER Ca2+ 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 Ca2+ uptake by mitochondria...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747567/modulation-of-the-nur77-bcl-2-apoptotic-pathway-by-p38%C3%AE-mapk
#10
Jie Liu, Guang-Hui Wang, Ying-Hui Duan, Yi Dai, Yuzhou Bao, Mengjie Hu, Yu-Qi Zhou, Mingyu Li, Fuquan Jiang, Hu Zhou, Xin-Sheng Yao, Xiao-Kun Zhang
Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2 pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2 pathway by CCE9 was associated with its activation of p38α MAPK...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/27900028/tumor-necrosis-factor-%C3%AE-induced-protein-8-like-1-promotes-apoptosis-by-regulating-b-cell-leukemia-lymphoma-2-family-proteins-in-raw264-7-cells
#11
Yinan Wang, Yao Liu, Chunfang Hu, Xiaoyan Ni, Xiaobo Huang
Although the newly identified protein tumor necrosis factor α-induced protein 8-like 1 (TNFAIP8L1), also known as TIPE1, has been reported to be able to induce apoptosis in human hepatocellular carcinoma cells, the involvement of TIPE1 in apoptosis remains to be elucidated. The present study investigated the pro-apoptotic effect of TIPE1 in an murine macrophage cell line, RAW264.7. The cell apoptosis rate was detected by flow cytometry. The results revealed that overexpressed TIPE1 could directly enhance the apoptosis and the cisplatin-induced cell death of RAW264...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27498846/physiological-and-pharmacological-control-of-bak-bax-and-beyond
#12
REVIEW
Mark P A Luna-Vargas, Jerry Edward Chipuk
Cellular commitment to the mitochondrial pathway of apoptosis is accomplished when proapoptotic B cell chronic lymphocytic leukemia/lymphoma (BCL)-2 proteins compromise mitochondrial integrity through the process of mitochondrial outer membrane permeabilization (MOMP). For nearly three decades, intensive efforts focused on the identification and interactions of two key proapoptotic BCL-2 proteins: BCL-2 antagonist killer (BAK) and BCL-2-associated X (BAX). Indeed, we now have critical insights into which BCL-2 proteins interact with BAK/BAX to either preserve survival or initiate MOMP...
December 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27447597/protocatechualdehyde-induces-s-phase-arrest-and-apoptosis-by-stimulating-the-p27-kip1-cyclin-a-d1-cdk2-and-mitochondrial-apoptotic-pathways-in-ht-29-cells
#13
Shi Zhong, You-Gui Li, Dong-Feng Ji, Tian-Bao Lin, Zhi-Qiang Lv
Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner...
July 19, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27308607/death-by-a-thousand-knives-multiple-bh3-only-proteins-are-required-for-maximal-apoptosis-triggered-through-the-bcr
#14
Matthew J Carter, Mark S Cragg
The B-cell receptor (BCR) represents a key driver of B-cell development. Consequently, multiple mechanisms link inappropriate BCR signaling to apoptosis. Recently, we characterized the molecular regulators involved in lymphoma cells, confirming a major role for Bcl-2 interacting mediator of cell death (Bim) and supplementary roles for Bcl-2 interacting killer (Bik) and Noxa, and showing that all 3 proteins are required for maximal apoptosis.
March 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27159560/allosteric-inhibition-of-antiapoptotic-mcl-1
#15
Susan Lee, Thomas E Wales, Silvia Escudero, Daniel T Cohen, James Luccarelli, Catherine G Gallagher, Nicole A Cohen, Annissa J Huhn, Gregory H Bird, John R Engen, Loren D Walensky
MCL-1 is an antiapoptotic BCL-2 family protein that has emerged as a major pathogenic factor in human cancer. Like BCL-2, MCL-1 bears a surface groove whose function is to sequester the BH3 killer domains of proapoptotic BCL-2 family members, a mechanism harnessed by cancer cells to establish formidable apoptotic blockades. Although drugging the BH3-binding groove has been achieved for BCL-2, translating this approach to MCL-1 has been challenging. Here, we report an alternative mechanism for MCL-1 inhibition by small-molecule covalent modification of C286 at a new interaction site distant from the BH3-binding groove...
June 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27120789/the-pro-apoptotic-paradox-the-bh3-only-protein-bcl-2-interacting-killer-bik-is-prognostic-for-unfavorable-outcomes-in-breast-cancer
#16
Vrajesh Pandya, Darryl Glubrecht, Larissa Vos, John Hanson, Sambasivarao Damaraju, John Mackey, Judith Hugh, Ing Swie Goping
Breast cancer is the leading cause of cancer-associated deaths in women worldwide. Clinical biomarkers give information on disease progression and identify relevant biological pathways. A confounding factor that uncouples markers from disease outcome is the ability of tumor cells to mutate and evade clinical intervention. Therefore, we focussed on apoptotic genes that modulate tumor regression. Using gene and tissue microarray analyses, we identified an association of Bcl-2 interacting killer (Bik) with poor breast cancer prognosis...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/26998897/whole-exome-sequencing-of-duodenal-adenocarcinoma-identifies-recurrent-wnt-%C3%AE-catenin-signaling-pathway-mutations
#17
Wei Yuan, Zhou Zhang, Binghua Dai, Qing Wei, Jinjin Liu, Yuzhen Liu, Yun Liu, Lin He, Daizhan Zhou
BACKGROUND: Genomic alterations of small bowel cancers remain poorly understood due to the rarity of these diseases. In the current study, the authors report the identification of somatic mutations from patients with duodenal adenocarcinoma by whole-exome sequencing. METHODS: Whole-exome sequencing and follow-up analysis were conducted in 12 matched tumor-normal tissue duodenal adenocarcinoma tissue pairs to examine the genetic characteristics of this disease. Somatic mutations (single-nucleotide variants and short insertion/deletions) were obtained and filtered and then searched for recurrently mutated genes and pathways...
June 1, 2016: Cancer
https://www.readbyqxmd.com/read/26841353/activation-induced-killer-cell-immunoglobulin-like-receptor-3dl2-binding-to-hla-b27-licenses-pathogenic-t-cell-differentiation-in-spondyloarthritis
#18
Anna Ridley, Hiroko Hatano, Isabel Wong-Baeza, Jacqueline Shaw, Katherine K Matthews, Hussein Al-Mossawi, Kristin Ladell, David A Price, Paul Bowness, Simon Kollnberger
OBJECTIVE: In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA-B27 and the phenotype and function of KIR-3DL2-expressing CD4+ T cells in SpA. METHODS: In total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27- and 8 B27+), and 9 patients with rheumatoid arthritis were studied...
April 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/26622468/bortezomib-inhibits-cell-proliferation-in-prostate-cancer
#19
Ren-Ping Zheng, Wei Wang, Chuan-Dong Wei
Despite the improvement in chemotherapeutic agents, the outcome of patients with prostate cancer remains poor. It is therefore imperative that new anticancer drugs are explored. The aim of the present study was to investigate the inhibitory effect of bortezomib on DU145 prostate cancer cells. The DU145 cell proliferation rate was detected via MTT assay prior to and following exposure to various concentrations of bortezomib, and the level of cell apoptosis and the cell cycle distribution were tested using flow cytometry...
September 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26610208/in-non-transformed-cells-bak-activates-upon-loss-of-anti-apoptotic-bcl-xl-and-mcl-1-but-in-the-absence-of-active-bh3-only-proteins
#20
D Senft, A Weber, F Saathoff, C Berking, M V Heppt, C Kammerbauer, S Rothenfusser, S Kellner, Z Kurgyis, R Besch, G Häcker
Mitochondrial apoptosis is controlled by proteins of the B-cell lymphoma 2 (Bcl-2) family. Pro-apoptotic members of this family, known as BH3-only proteins, initiate activation of the effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), which is counteracted by anti-apoptotic family members. How the interactions of Bcl-2 proteins regulate cell death is still not entirely clear. Here, we show that in the absence of extrinsic apoptotic stimuli Bak activates without detectable contribution from BH3-only proteins, and cell survival depends on anti-apoptotic Bcl-2 molecules...
2015: Cell Death & Disease
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