National Bureau of Economic Research (NBER)
Haihao Ma, Xiumei Yan, Lin Yan, Jingyan Zhao, Jiping Song, Rong Peng, Yongbo Yang, Jianxin Peng, Kaiyu Liu,
Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule, essential for activating initiator caspase and downstream effector caspases, which directly cause apoptosis. In fruit flies, nematodes, and mammals, Apaf-1 has been extensively studied. However, the structure and function of Apaf-1 in Lepidoptera remain unclear. This study identified a novel Apaf-1 from Spodoptera litura, named Sl-Apaf-1. Sl-Apaf-1 contains three domains: a CARD domain, as ... WD motifs, and is very similar to mammalian Apaf-1. Interference of Sl-apaf-1 expression in ...
Tópico(s): Trace Elements in Health
2021 - Multidisciplinary Digital Publishing Institute | Insects
Ali-Reza Noori, Amin Tashakor, Maryam Nikkhah, Leif A. Eriksson, Saman Hosseinkhani, Howard O. Fearnhead,
... investigate the effect of WD domain deletion on Apaf-1 oligomerization. Apaf-1 is an adaptor molecule in formation of ... cell death pathway. Structural studies suggest that normally Apaf-1 is held in an inactive conformation by intramolecular interactions between Apaf-1's nucleotide binding domain and one of ... WD40 domains (WD1). In the prevailing model of Apaf-1 activation, cytochrome c binds to sites in WD1 and in Apaf-1's second WD40 domain (WD2), moving WD1 ... away from the nucleotide binding domain. This allows Apaf-1 to bind dATP or ATP and to ...
Tópico(s): ATP Synthase and ATPases Research
2020 - Elsevier BV | Biochimie
Hongjie Wang, Juan Zhu, Liping Jiang, Boying Shan, Peihan Xiao, Jiayi Ai, Na Li, Feng Qi, Siyun Niu,
... mitochondrial pathway [15]. Apoptotic protease activating factor-1 (Apaf-1) is a major component of the apoptotic ... in the mitochondrial apoptotic pathway, this study used Apaf-1 as a target to explore the mechanism by which Heshouwuyin inhibits the Apaf-1 pathway of spermatogenic cell apoptosis.In this ... germ cells and the inhibitory effect of Heshouwuyin. Apaf-1 was specifically knocked down by siRNA interference ... did not change significantly after specific knockdown of Apaf-1, and the mRNA and protein expression levels ...
Tópico(s): Toxin Mechanisms and Immunotoxins
2020 - BioMed Central | BMC Complementary Medicine and Therapies
Ali Noori, Elaheh Sadat Hosseini, Maryam Nikkhah, Saman Hosseinkhani,
Apaf-1 is a cytosolic multi-domain protein in the apoptosis regulatory network. When cytochrome c releases ... mitochondria; it binds to WD-40 repeats of Apaf-1 molecule and induces oligomerization of Apaf-1. Here in, a split luciferase assay was ... free and cell-based systems. This assay uses Apaf-1 tagged with either N-terminal fragment or ... formation is induced inside the cells which express Apaf-1 tagged with complementary fragments of luciferase while ... dependent luciferase activity was observed with full length Apaf-1. However, luciferase activity due to apoptosome formation ...
Tópico(s): RNA Interference and Gene Delivery
2018 - Elsevier BV | Archives of Biochemistry and Biophysics
While earlier studies of Apaf-1 holo-apoptosome architecture revealed the spectacular heptameric wheel-like structure formed by Apaf-1, the central CARD disk responsible for caspase- ... describe a crystal structure of the complex between Apaf-1 CARD and caspase-9 CARD. Together with ... of the holo-apoptosome. While earlier studies of Apaf-1 holo-apoptosome architecture revealed the spectacular heptameric wheel-like structure formed by Apaf-1, the central CARD disk responsible for caspase- ... describe a crystal structure of the complex between Apaf-1 CARD and caspase-9 CARD. Together with ...
Tópico(s): PARP inhibition in cancer therapy
2017 - Elsevier BV | Structure
Jemma Wu, Dana Pascovici, Vera Ignjatović, Xiaomin Song, Christoph Krisp, Mark P. Molloy,
... Wu, Jemma X. Wu Australian Proteome Analysis Facility (APAF), Department of Chemistry and Biomolecular Sciences, Macquarie University, ... authorDana Pascovici, Dana Pascovici Australian Proteome Analysis Facility (APAF), Department of Chemistry and Biomolecular Sciences, Macquarie University, ... authorXiaomin Song, Xiaomin Song Australian Proteome Analysis Facility (APAF), Department of Chemistry and Biomolecular Sciences, Macquarie University, ... authorChristoph Krisp, Christoph Krisp Australian Proteome Analysis Facility (APAF), Department of Chemistry and Biomolecular Sciences, Macquarie University, ...
Tópico(s): Metabolomics and Mass Spectrometry Studies
2017 - Wiley | PROTEOMICS
Daria N. Shalaeva, Daria V. Dibrova, Michael Y. Galperin, Armen Y. Mulkidjanian,
... mitochondria, to the apoptotic protease activating factor 1 (Apaf-1) is a key event in the apoptotic ... The binding triggers a major domain rearrangement in Apaf-1, which leads to oligomerization of Apaf-1/cytochrome c complexes into an apoptosome. Despite ... availability of crystal structures of cytochrome c and Apaf-1 and cryo-electron microscopy models of the ... apoptosome, the binding mode of cytochrome c to Apaf-1, as well as the nature of the amino acid residues of Apaf-1 involved remain obscure.We investigated the interaction ...
Tópico(s): Lipid Membrane Structure and Behavior
2015 - BioMed Central | Biology Direct
Raheleh Shakeri, Saman Hosseinkhani, Marek Łoś, Jamshid Davoodi, Mayur Vilas Jain, Artur Cieślar‐Pobuda, Mehrdad Rafat, Sussan Kaboudanian Ardestani,
Apaf-1, the key element of apoptotic mitochondrial pathway normally rests in an autoinhibited form inside the ... release from the mitochondria and its binding to Apaf-1 is required to transform the "closed" (inactive) molecule to open form.WRD-domain of Apaf-1 has a critical role in the preservation ... are involved in maintaining the inactive configuration of Apaf-1.At the present study, we have investigated ... of auto-inhibited form of full length human Apaf-1.E546residue is mutated to glutamine (Q) and ... evaluated.Overexpression of wild type, E546Q and E546R Apaf-1 in HEK293T cells does not induce apoptosis ...
Tópico(s): ATP Synthase and ATPases Research
2015 - Elsevier BV | International Journal of Biological Macromolecules
Xiaowen Zhang, Ning Liu, Sheng Chen, Ye Wang, Kailai Sun, Zhen‐Ming Xu, FU Wei-neng,
... for laryngeal cancer. Apoptotic protease activating factor 1 (APAF-1) was recently demonstrated to be a target ... However, whether miR-23a exerts its effects via APAF-1 in laryngeal cancer, remains unknown. In the ... reverse transcription-quantitative polymerase chain reaction (RT-qPCR). APAF-1 mRNA and protein expression levels were assayed ... western blotting, respectively. Binding of miR-23a to APAF-1 was monitored by a luciferase reporter assay. ... to investigate the roles of miR-23a and APAF-1 in Hep2 cell proliferation and apoptosis. miR- ...
Tópico(s): RNA Interference and Gene Delivery
2015 - Spandidos Publishing | Oncology Letters
Léonard Jagot-Lacoussiere, Audrey Faye, Heriberto Bruzzoni‐Giovanelli, Bruno O. Villoutreix, Jean‐Christophe Rain, Jean‐Luc Poyet,
... death pathway, the apoptotic protease activating factor 1 (Apaf-1) is involved in the DNA damage response ... non-apoptotic function requires a nuclear translocation of Apaf-1 during the G1-to-S transition. However, the mechanisms that trigger the nuclear accumulation of Apaf-1 upon DNA damage remain to be investigated. ... we show that the main 4 isoforms of Apaf-1 can undergo nuclear translocation and restore Apaf-1 deficient MEFs cell cycle arrest in the ... 1. Interestingly, DNA damage-dependent nuclear accumulation of Apaf-1 occurs independently of p53 and the retinoblastoma ( ...
Tópico(s): DNA Repair Mechanisms
2015 - Taylor & Francis | Cell Cycle
Jonathan Martínez‐Fábregas, Irene Díaz‐Moreno, Katiuska González‐Arzola, Simon Janocha, José A. Navarro, Manuel Hervás, Rita Bernhardt, Antonio Díaz‐Quintana, Miguel Á. De la Rosa,
... protease-activating factor-1CED-4cell death abnormality-4DarkDrosophila Apaf-1-related killerBiFCBimolecular fluorescence complementationCPTCamptothecinSPRsurface plasmon resonanceNAAnaphthalene acetic ... protease-activating factor-1CED-4cell death abnormality-4DarkDrosophila Apaf-1-related killerBiFCBimolecular fluorescence complementationCPTCamptothecinSPRsurface plasmon resonanceNAAnaphthalene acetic ... activating factor-1 cell death abnormality-4 Drosophila Apaf-1-related killer Bimolecular fluorescence complementation Camptothecin surface ...
Tópico(s): Cell death mechanisms and regulation
2013 - Elsevier BV | Molecular & Cellular Proteomics
Shucheng Gu, Youshan Zhao, Juan Guo, Feng Xu, Chengming Fei, Xi Zhang, Chao Xiao, Chunkang Chang, Li Xiao,
Apoptotic protease-activating factor 1 (APAF-1) is a central component of the intrinsic pathway of apoptosis. Our study aims at searching the role of APAF-1 in iron overload myelodysplastic syndrome (MDS). Erythroid apoptosis rate, mRNA expression levels of APAF-1, and caspase-9 activity were determined by ... to observe the alteration in erythrocyte apoptosis rate, APAF-1 mRNA, and protein expression levels. Moreover, as control, erythroid apoptosis rate and APAF-1 mRNA expression were detected after silencing APAF- ...
Tópico(s): Trace Elements in Health
2013 - SAGE Publishing | Tumor Biology
Shujun Yuan, Christopher W. Akey,
Apaf-1-like molecules assemble into a ring-like platform known as the apoptosome. This cell death ... death pathway. In this review, crystal structures of Apaf-1 monomers and CED-4 dimers have been ... caspase recognition domains (CARDs) of procaspase-9 and Apaf-1 interact with each other to form a ... of this critical activation process on the apoptosome. Apaf-1-like molecules assemble into a ring-like ... death pathway. In this review, crystal structures of Apaf-1 monomers and CED-4 dimers have been ... caspase recognition domains (CARDs) of procaspase-9 and Apaf-1 interact with each other to form a ...
Tópico(s): Phagocytosis and Immune Regulation
2013 - Elsevier BV | Structure
Y-S Zang, Y-F Zhong, Fang Zheng, Bo Li, Jing An,
... apoptosis and DNA damage through the regulation of Apaf-1 and is thus involved in the development ... measured the expression of miR-155 and the Apaf-1 protein in lung cancer tissues. The results ... tissues than in paracancerous and normal tissues; whereas Apaf-1 expression was lower in the lung cancerous tissues. We then established miR-155-silenced and Apaf-1-overexpressed A549 cell lines by transfection with pMAGic2.0-BIC-siRNA and pcDNA3.1-Apaf-1, respectively. These cell lines were then treated ... miR-155 resulted in elevated expression of the Apaf-1 protein, whereas Apaf-1 mRNA levels remained ...
Tópico(s): RNA Research and Splicing
2012 - Springer Nature | Cancer Gene Therapy
Andrea Newbold, Stephin J. Vervoort, Benjamin P. Martin, Michael Bots, Ricky W. Johnstone,
... recently demonstrated that Eμ-myc lymphomas devoid of Apaf-1 displayed a delayed cell death in response to HDACi treatment, and loss of Apaf-1 failed to affect therapeutic efficacy.5 The ... role in regulating the response of Eμ-myc/Apaf-1−/− cells to HDACi, we knocked down the ... treated Atg5- and Atg7-shRNA-expressing Eμ-myc/Apaf-1−/− lymphomas with vorinostat and determined the ratio ... LC3-II by western blot. In Eμ-myc/Apaf-1−/− cells with decreased expression of Atg5 or ... to induce tumor cell death in Eμ-myc/Apaf-1−/− lymphomas. (a) Eμ-myc/Apaf-1−/− lymphomas ...
Tópico(s): Autophagy in Disease and Therapy
2012 - Springer Nature | Cell Death and Disease
Jiyeon Kim, Amanda B. Parrish, Manabu Kurokawa, Kenkyo Matsuura, Christopher D. Freel, Joshua L. Andersen, Carrie E. Johnson, Sally Kornbluth,
... mediated phosphorylation and 14-3-3ε binding of Apaf-1 suppresses cytochrome c-induced apoptosis Jiyeon Kim ... a novel mode of apoptotic regulation exerted through Apaf-1 phosphorylation by the 90-kDa ribosomal S6 ... cell types promoted 14-3-3ε binding to Apaf-1 and rendered the cells insensitive to cytochrome ... apoptosomal regulation wherein MAPK signalling promotes Rsk-catalysed Apaf-1 phosphorylation and consequent binding of 14-3- ... formation, cytosolic cytochrome c binds the adaptor protein Apaf-1, inducing a conformational change and dATP hydrolysis ...
Tópico(s): ATP Synthase and ATPases Research
2012 - Springer Nature | The EMBO Journal
Andreas Strasser, Suzanne Cory, Jerry M. Adams,
... proteolytic cascade often initiates on the scaffold protein APAF-1 (Zou et al, 1997), which proved to ... apoptosis inducers (EGL-1), of the caspase-activator Apaf-1 (CED-4) and of the proteolytic caspases ( ... whereas vertebrate Bcl-2 does not bind to Apaf-1 but instead prevents the activation of its ... cytochrome c (cyt c), an essential cofactor for Apaf-1. Download figure Download PowerPoint This review will ... scaffold proteins (FADD/Mort1 for caspase-8 and Apaf-1 for caspase-9; Figure 2), where conformational ...
Tópico(s): Autophagy in Disease and Therapy
2011 - Springer Nature | The EMBO Journal
Xinchen Teng, J. Marie Hardwick,
... assembly of a heptameric wheel-like complex of Apaf-1 molecules known as the apoptosome. Once assembled ... of CED-4, the Caenorhabditis elegans ortholog of Apaf-1. CED-4 and Apaf-1 belong to a new class of signal ... structure, rather than the flat structure proposed for Apaf-1. For now, the only available crystal structure of Apaf-1 is for the inhibited (ADP-bound) monomer, ... 933Crossref PubMed Scopus (269) Google Scholar). A heptameric Apaf-1 apoptosome structure was previously obtained by cryoelectron ... structure of individual domains from the inhibited monomeric Apaf-1 into this EM structure of the Apaf- ...
Tópico(s): Autophagy in Disease and Therapy
2010 - Cell Press | Cell
Reza Behjati, Koji Kawai, Yukinori Inadome, Junko Kano, Hideyuki Akaza, Masayuki Noguchi,
Apoptotic protease activating factor-1 (APAF-1) is a key regulator gene of apoptosis, located downstream from p53. Loss of APAF-1 expression is associated with chemorefractory malignant melanoma ... In order to make clear the function of APAF-1 in the carcinogenesis of germ cell tumors, we evaluated the expression levels of APAF-1 and several apoptosis and differentiation markers by ... apoptotic reactivity, tumor differentiation, and proliferation activity, respectively. APAF-1 was downregulated in two TGCT cell lines ...
Tópico(s): Renal and related cancers
2010 - Wiley | Cancer Science
Lijun Tan, Roland P.S. Kwok, Abhishek Shukla, Malti Kshirsagar, Lili Zhao, Anthony W. Opipari, J. Rebecca Liu,
... for expression and function of the apoptosome components Apaf‐1 and caspase‐9. Expression levels were analyzed by immunohistochemistry and immunoblotting; Apaf‐1 function was determined by assessing the ability of endogenous Apaf‐1 to cleave caspase‐9 in the presence ... of the histone deacetylase inhibitor trichostatin A on Apaf‐1 expression and function was evaluated. RESULTS: The ... of chemotherapy is due in part to deficient Apaf‐1 activity. Although Apaf‐1 is expressed in most ovarian cancers, the ...
Tópico(s): Protein Degradation and Inhibitors
2010 - Wiley | Cancer
Bülent Erol, Murat Bozlu, Volkan Hancı, Hüsnü Tokgöz, Sibel Bektaş, Görkem Mungan,
... Ab-1, and apoptosis protease–activating factor 1 (APAF-1) antibody (Lab Vision Corp., Neomarkers, CA), respectively ( ... of testicular MDA levels and iNOS, eNOS, and APAF-1 expressions of each group are shown in ... MDA levels and expressions of iNOS, eNOS, and APAF-1 obtained from the T-D group were ... Ipsilateral testicular MDA levels and iNOS, eNOS, and APAF-1 expressions obtained from the CoQ10 treatment group ... values of MDA levels and iNOS, eNOS and APAF-1 expressions in ipsilateral and contralateral testes (mean ± ...
Tópico(s): Aldose Reductase and Taurine
2009 - Elsevier BV | Fertility and Sterility
Akiomi Nagasaka, Kohki Kawane, Hiroki Yoshida, Shigekazu Nagata,
... during mouse development. Here, we showed that an Apaf-1-null mutation in the DNase II−/− embryos ... of macrophages carrying undigested DNA were present in Apaf-1−/− embryos, indicating that cells died and were engulfed in an Apaf-1-independent manner. In most tissues of the Apaf-1−/− embryos, no processed caspase-3 was detected, ... cells were found in the tail of the Apaf-1−/− embryos, suggesting that the Apaf-1-independent programmed cell death occurred, and these ... 3 was detected in E14.5 thymus of Apaf-1−/− embryos. Treatment of fetal thymocytes with staurosporine, ...
Tópico(s): Autophagy in Disease and Therapy
2009 - Springer Nature | Cell Death and Differentiation
Wei Pan, Li S. da Graca, Yufang Shao, Qian Yin, Hao Wu, Xuejun Jiang,
... Google Scholar). The released cytochrome c binds to Apaf-1, the essential mediator of the pathway, and ... PubMed Scopus (238) Google Scholar). Subsequently, the activated Apaf-1 protein forms a multimeric protein complex called ... mitochondria during apoptosis. Further, nucleotide binding/exchanging of Apaf-1, a key biochemical event of the pathway, ... also closely regulated. Recently, we found that the Apaf-1-dependent caspase activation can be enhanced by ... HSP70, function as the nucleotide exchange factor for Apaf-1, a mechanism reminiscent of G protein regulation ( ...
Tópico(s): Ubiquitin and proteasome pathways
2009 - Elsevier BV | Journal of Biological Chemistry
Qingping Xu, Christopher L. Rife, Dennis Carlton, Mitchell D. Miller, Sanjeev Krishna, Marc‐André Elsliger, Polat Abdubek, Tamara Astakhova, Hsiu‐Ju Chiu, Thomas Clayton, Lian Duan, Julie Feuerhelm, Slawomir K. Grzechnik, Joanna Hale, Gye Won Han, Lukasz Jaroszewski, Kevin K. Jin, Heath E. Klock, Mark W. Knuth, Abhinav Kumar, Daniel McMullan, Andrew T. Morse, Edward Nigoghossian, Linda Okach, Silvya Oommachen, Jessica Paulsen, Ron Reyes, Henry van den Bedem, Keith O. Hodgson, John Wooley, Ashley M. Deacon, Adam Godzik, Scott A. Lesley, Ian A. Wilson,
... apoptotic)-ATPases5 (e.g., animal apoptosis regulators CED4/Apaf-1, plant disease resistance proteins, and bacterial AfsR- ... structures are currently known: the cell death regulators Apaf-1 and CED-4.7, 8 Here, we ... 4 (PDB 2a5y, Z = 17.2),8 and Apaf-1 (PDB 1z6t, Z = 12.0),7 bacterial ... possess the typical AAA+ sensor II motif. The Apaf-1 structure suggests that an equivalent sensor II ... 2(B)]. Additionally, the potential sensor II of Apaf-1 (His438) is not conserved in SSO1545. Thus, ... PDB 1w5t),29 and apoptotic protease activating factor Apaf-1 (PDB 1z6t).7 The overall structures of ...
Tópico(s): Cell death mechanisms and regulation
2008 - Wiley | Proteins Structure Function and Bioinformatics
Deborah Wallace, Thomas G. Cotter,
Abstract Apaf‐1 and the cysteine proteases known as caspases are genes central to the intrinsic apoptotic pathway in ... have shown that histone deacetylase (HDAC) activity regulates Apaf‐1 expression in the retina. In this study, ... detailed molecular mechanism of HDAC‐mediated regulation of Apaf‐1 initially by use of a cell line ( ... HDAC activity by trichostatin A (TSA) up‐regulates Apaf‐1 expression, which precedes the induction of apoptosis. ... 1 and p53 binding sites on the mouse Apaf‐1 promoter and show by chromatin immunoprecipitation assays ...
Tópico(s): NF-κB Signaling Pathways
2008 - Wiley | Journal of Neuroscience Research
Roberto Sánchez‐Olea, Sara Ortiz, Odmara L. Barreto Chang, Qing Yang, Chijie Xu, Hong Zhu, Junying Yuan,
... cell cycle progression and apoptosis. Parcs interacted with Apaf-1 by binding to the oligomerization domain of Apaf-1. Apaf-1-mediated activation of caspase-9 and caspase- ... cell cycle progression and apoptosis. Parcs interacted with Apaf-1 by binding to the oligomerization domain of Apaf-1. Apaf-1-mediated activation of caspase-9 and caspase- ... normal cells that is lost in tumor cells. Apaf-1 (apoptotic protease-activating factor 1), a mammalian ... of the apoptosome. Mouse embryonic fibroblasts deficient in apaf-1 or expressing a mutant allele of cytochrome ...
Tópico(s): Phagocytosis and Immune Regulation
2008 - Elsevier BV | Journal of Biological Chemistry
Shahul Mouhamad, Lorenzo Galluzzi, Yaël Zermati, Maria Castedo, Guido Kroemer,
Apaf-1 is an essential component of the apoptosome, the molecular complex assembled in response to mitochondrial cytochrome c release that promotes caspase activation. Apaf-1 expression is suppressed in some malignant tumors, ... and colorectal carcinoma, in which the loss of Apaf-1 expression marks tumor progression and poor prognosis. Recent results from our laboratory demonstrate that Apaf-1 has an apoptosis-unrelated function that may ... role as a tumor suppressor. The knockout of apaf-1 (in mice), the knockdown of Apaf-1 ( ...
Tópico(s): Cell death mechanisms and regulation
2007 - Taylor & Francis | Cell Cycle
Qazi M. Ashraf, Om P. Mishra, Maria Delivoria‐Papadopoulos,
Apoptotic protease activating factor-1 (Apaf-1) is a critical regulator of apoptosis and a crucial part of the apoptosome that is assembled in response to several ... nuclear apoptotic proteins. The present study investigates that Apaf-1 is expressed during hypoxia in the cerebral ... clonidine prevents the hypoxia induced increase expression of Apaf-1. Studies were conducted in 19 newborn piglets, ... SDS-PAGE and probed with specific antibodies to Apaf-1. The expression of Apaf-1 in neuronal nuclei was 48.86+/-5. ...
Tópico(s): ATP Synthase and ATPases Research
2007 - Elsevier BV | Neuroscience Letters