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Bcl interacting killer

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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
#1
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
#2
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
#3
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...
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/26567849/comprehensive-functional-characterization-of-cancer-testis-antigens-defines-obligate-participation-in-multiple-hallmarks-of-cancer
#11
Kimberly E Maxfield, Patrick J Taus, Kathleen Corcoran, Joshua Wooten, Jennifer Macion, Yunyun Zhou, Mark Borromeo, Rahul K Kollipara, Jingsheng Yan, Yang Xie, Xian-Jin Xie, Angelique W Whitehurst
Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling...
November 16, 2015: Nature Communications
https://www.readbyqxmd.com/read/26182360/%C3%A2-np73-is-capable-of-inducing-apoptosis-by-co-ordinately-activating-several-bh3-only-proteins
#12
Dámaso Sánchez-Carrera, Mikel García-Puga, Lucrecia Yáñez, Íñigo Romón, Carlos Pipaón
Inactivation of p53 is one of the most relevant events in human cancer, since it allows transformed cells to escape their own proliferation control and leave them irresponsive to drugs that aim to damage their DNA. When p53 falls, other members of its family may become targets to attack tumoural cells. p73 has shown capacity to mediate these attacks. However, its N-terminal truncated isoforms have been associated with oncogenesis due to their capacity to act as dominant negatives of p53 and the transactivation (TA) isoforms of p73...
2015: Bioscience Reports
https://www.readbyqxmd.com/read/26171069/synergistic-effects-of-cisplatin-and-proteasome-inhibitor-bortezomib-on-human-bladder-cancer-cells
#13
Ece Konac, Nuray Varol, Ilker Kiliccioglu, Cenk Y Bilen
The proteasome inhibitor bortezomib is a promising novel agent in bladder cancer therapy; however, inducible cytoprotective mechanisms may limit its potential efficacy. To date, the cellular and molecular effects of proteasome inhibitors on bladder cancer cells have been poorly characterized. Despite the consistent rate of initial responses, cisplatin treatment typically results in the development of chemoresistance, leading to therapeutic failure. Therefore, the present study aimed to characterize the molecular mechanisms underlying the anti-proliferative effects of cisplatin and bortezomib combination therapy on the human T24 bladder cancer cell line, by analyzing the protein expression levels of apoptotic genes...
July 2015: Oncology Letters
https://www.readbyqxmd.com/read/25733819/a-computational-and-functional-study-elicits-the-ameliorating-effect-of-the-chinese-herbal-formula-huo-luo-xiao-ling-dan-on-experimental-ischemia-induced-myocardial-injury-in-rats-via-inhibition-of-apoptosis
#14
Xiang-Dong Han, Zhi-Wei Zhou, Wei Yang, Hang-Cheng Ye, Ying-Zi Xu, Yun-Feng Huang, Tong Zhang, Shu-Feng Zhou
Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear...
2015: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/25714678/distinct-lipid-effects-on-tbid-and-bim-activation-of-membrane-permeabilization-by-pro-apoptotic-bax
#15
Aisha Shamas-Din, Scott Bindner, Xiaoke Chi, Brian Leber, David W Andrews, Cécile Fradin
After exposure to stressful stimuli, apoptotic signals can be relayed to mitochondria by pro-apoptotic activator proteins, tBid (truncated Bid/p15) and Bim (Bcl-2 interacting mediator), which activate Bax (Bcl-2 associated X protein) and or Bak (Bcl-2 antagonist/killer) to induce mitochondrial outer membrane (MOM) permeabilization (MOMP). These protein-protein and protein-membrane interactions are critical for apoptosis regulation, since MOMP irreversibly leads to cell death. Whereas the distinct roles of tBid and Bim as sensors of different types of stress are well recognized, it is not known whether the molecular mechanisms whereby they initiate MOMP are the same...
May 1, 2015: Biochemical Journal
https://www.readbyqxmd.com/read/25565426/bh3-only-proteins-a-20-year-stock-take
#16
REVIEW
Marcel Doerflinger, Jason A Glab, Hamsa Puthalakath
BH3-only proteins are the sentinels of cellular stress, and their activation commits cells to apoptosis. Since the discovery of the first BH3-only protein BAD almost 20 years ago, at least seven more BH3-only proteins have been identified in mammals. They are regulated by a variety of environmental stimuli or by developmental cues, and play a crucial role in cellular homeostasis. Some are considered to be tumor suppressors, and also play a significant role in other pathologies. Their non-apoptotic functions are controversial, but there is broad consensus emerging regarding their role in apoptosis, which may help in designing better therapeutic agents for treating a variety of human diseases...
March 2015: FEBS Journal
https://www.readbyqxmd.com/read/25482509/mitochondrial-shape-governs-bax-induced-membrane-permeabilization-and-apoptosis
#17
Thibaud T Renault, Konstantinos V Floros, Rana Elkholi, Kelly-Ann Corrigan, Yulia Kushnareva, Shira Y Wieder, Claudia Lindtner, Madhavika N Serasinghe, James J Asciolla, Christoph Buettner, Donald D Newmeyer, Jerry E Chipuk
Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size...
January 8, 2015: Molecular Cell
https://www.readbyqxmd.com/read/25462348/ectromelia-virus-encodes-an-anti-apoptotic-protein-that-regulates-cell-death
#18
Ninad Mehta, John Taylor, Douglas Quilty, Michele Barry
Apoptosis serves as a powerful defense against damaged or pathogen-infected cells. Since apoptosis is an effective defense against viral infection, many viruses including poxviruses, encode proteins to prevent or delay apoptosis. Here we show that ectromelia virus, the causative agent of mousepox encodes an anti-apoptotic protein EVM025. Here we demonstrate that expression of functional EVM025 is crucial to prevent apoptosis triggered by virus infection and staurosporine. We demonstrate that the expression of EVM025 prevents the conformational activation of the pro-apoptotic proteins Bak and Bax, allowing the maintenance of mitochondrial membrane integrity upon infection with ECTV...
January 15, 2015: Virology
https://www.readbyqxmd.com/read/25371206/the-functional-differences-between-pro-survival-and-pro-apoptotic-b-cell-lymphoma-2-bcl-2-proteins-depend-on-structural-differences-in-their-bcl-2-homology-3-bh3-domains
#19
Erinna F Lee, Grant Dewson, Marco Evangelista, Anne Pettikiriarachchi, Grace J Gold, Haoran Zhu, Peter M Colman, W Douglas Fairlie
Bcl-2 homology 3 (BH3) domains are short sequence motifs that mediate nearly all protein-protein interactions between B cell lymphoma 2 (Bcl-2) family proteins in the intrinsic apoptotic cell death pathway. These sequences are found on both pro-survival and pro-apoptotic members, although their primary function is believed to be associated with induction of cell death. Here, we identify critical features of the BH3 domains of pro-survival proteins that distinguish them functionally from their pro-apoptotic counterparts...
December 26, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25318106/interaction-between-na-k-atpase-and-bcl-2-proteins-bclxl-and-bak
#20
Peter K Lauf, Tariq Alqahtani, Karin Flues, Jaroslaw Meller, Norma C Adragna
In silico analysis predicts interaction between Na-K-ATPase (NKA) and Bcl-2 protein canonical BH3- and BH1-like motifs, consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine, a BH3 mimetic, in fetal human lens epithelial cells (FHLCs) (Lauf PK, Heiny J, Meller J, Lepera MA, Koikov L, Alter GM, Brown TL, Adragna NC. Cell Physiol Biochem 31: 257-276, 2013). This report establishes proof of concept: coimmunoprecipitation and immunocolocalization showed unequivocal and direct physical interaction between NKA and Bcl-2 proteins...
January 1, 2015: American Journal of Physiology. Cell Physiology
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