Praf2 Is a Novel Bcl-xL/Bcl-2 Interacting Protein with the Ability to Modulate Survival of Cancer Cells

[ { "id": "2273125", "title": "Bcl-xL Affects Group A", "abstract": "Anti-apoptotic Bcl-2 and Bcl-xL are proposed to regulate starvation-induced autophagy by directly interacting with Beclin 1. Beclin 1 is also thought to be involved in multiple vesicle trafficking pathways such as endocytosis by binding to Atg14L and UVRAG. However, how the interaction of Bcl-2 family proteins and Beclin 1 regulates anti-bacterial autophagy (xenophagy) is still unclear. In this study, we analyzed these interactions using Group A Streptococcus (GAS; Streptococcus pyogenes) infection as a model. GAS is internalized into epithelial cells through endocytosis, while the intracellular fate of GAS is degradation by autophagy. Here, we found that Bcl-xL but not Bcl-2 regulates GAS-induced autophagy. Autophagosome-lysosome fusion and the internalization process during GAS infection were promoted in Bcl-xL knockout cells. In addition, knockout of Beclin 1 phenocopied the internalization defect of GAS. Furthermore, UVRAG interacts not only with Beclin 1 but also with Bcl-xL, and overexpression of UVRAG partially rescued the internalization defect of Beclin 1 knockout cells during GAS infection. Thus, our results indicate that Bcl-xL inhibits GAS-induced autophagy directly by suppressing autophagosome-lysosome fusion and indirectly by suppressing GAS internalization via interaction with Beclin 1-UVRAG.", "source_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170138", "doc_type": 4, "year": 2017, "issue": 1, "volume": 12, "first_page": 0, "last_page": 0, "citation_count": 0, "reference_count": 9, "venue": { "id": 2110000215, "name": "PLOS ONE", "abbr": "" }, "author": [ { "id": 1001977822, "name": "Shintaro Nakajima" }, { "id": 1001737543, "name": "Chihiro Aikawa" }, { "id": 1001977818, "name": "Takashi Nozawa" }, { "id": 1001977820, "name": "Atsuko Minowa-Nozawa" }, { "id": 1001977821, "name": "Hirotaka Toh" }, { "id": 1000795663, "name": "Ichiro Nakagawa" } ], "field": [ { "id": 2042859286, "name": "Producer gas" }, { "id": 2020037556, "name": "Natural-gas processing" }, { "id": 2007937117, "name": "Natural gas" }, { "id": 2011868470, "name": "Associated petroleum gas" }, { "id": 2034654568, "name": "Sour gas" }, { "id": 2010097079, "name": "Renewable natural gas" }, { "id": 2016162266, "name": "Natural-gas condensate" }, { "id": 2008840299, "name": "Gas holder" }, { "id": 2014995684, "name": "Streptococcus pyogenes" }, { "id": 2047880846, "name": "Compressor station" } ], "cite": [ { "name": "GB/T 7714", "text": "Nakajima Shintaro, Aikawa Chihiro, Nozawa Takashi, et al. Bcl-xL Affects Group A[J]. PLOS ONE, 2017, 12(1)." }, { "name": "MLA", "text": "Nakajima, Shintaro, et al. \"Bcl-xL Affects Group A\" PLOS ONE., vol. 12, no. 1, 2017." }, { "name": "APA", "text": "Nakajima Shintaro, Aikawa Chihiro, Nozawa Takashi, Minowa-Nozawa Atsuko, Toh Hirotaka, & Nakagawa Ichiro (2017). Bcl-xL Affects Group A. PLOS ONE, 12(1)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap2273125,\n title=\"Bcl-xL Affects Group A\",\n author=\"Shintaro {Nakajima} and Chihiro {Aikawa} and Takashi {Nozawa} and {Atsuko Minowa-Nozawa} and Hirotaka {Toh} and Ichiro {Nakagawa}\",\n journal=\"PLOS ONE\",\n volume=\"12\",\n number=\"1\",\n url=\"https://www.acemap.info/paper/2273125\",\n year=\"2017\"\n}" } ] }, { "id": "2371060", "title": "Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters", "abstract": "Iron–sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the NAF-1 cluster, NAF-1(H114C), in xenograft breast cancer tumors results in a dramatic decrease in tumor size that is accompanied by enhanced mitochondrial iron and reactive oxygen accumulation and reduced cellular tolerance to oxidative stress. Furthermore, treating breast cancer cells with pioglitazone that stabilizes the 3Cys-1His cluster of NAF-1 results in a similar effect on mitochondrial iron and reactive oxygen species accumulation. Taken together, our findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. Cluster transfer reactions mediated by the overexpressed NAF-1 protein are therefore critical for inducing oxidative stress tolerance in cancer cells, leading to rapid tumor growth, and drugs that stabilize the NAF-1 cluster could be used as part of a treatment strategy for cancers that display high NAF-1 expression.", "source_url": "https://www.pnas.org/content/113/39/10890", "doc_type": 4, "year": 2016, "issue": 39, "volume": 113, "first_page": 10890, "last_page": 10895, "citation_count": 7, "reference_count": 7, "venue": { "id": 2110000201, "name": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA", "abbr": "" }, "author": [ { "id": 1002420182, "name": "Merav Darash-Yahana" }, { "id": 1002562030, "name": "Yair Pozniak" }, { "id": 1001956242, "name": "Mingyang Lu" }, { "id": 1002420183, "name": "Yang-Sung Sohn" }, { "id": 1002420178, "name": "Ola Karmi" }, { "id": 1002420180, "name": "Sagi Tamir" }, { "id": 1001527154, "name": "Fang Bai" }, { "id": 1001210813, "name": "Luhua Song" }, { "id": 1001279316, "name": "Patricia A. Jennings" }, { "id": 1001677675, "name": "Eli Pikarsky" }, { "id": 1001240485, "name": "Tamar Geiger" }, { "id": 1001279317, "name": "José N. Onuchic" }, { "id": 1001210821, "name": "Ron Mittler" }, { "id": 1001279315, "name": "Rachel Nechushtai" } ], "field": [ { "id": 2018252668, "name": "Penile cancer" }, { "id": 2004556151, "name": "Appendix cancer" }, { "id": 2017571735, "name": "Migrastatin" }, { "id": 2008621301, "name": "Glomangioma" }, { "id": 2015533717, "name": "Glomus tumour" }, { "id": 2011716103, "name": "Halichondrin B" }, { "id": 2010169572, "name": "Mapatumumab" }, { "id": 2023692886, "name": "Glomangiosarcoma" }, { "id": 2035334641, "name": "Grifola frondosa" }, { "id": 2011263863, "name": "Adamantinoma" } ], "cite": [ { "name": "GB/T 7714", "text": "Darash-Yahana Merav, Pozniak Yair, Lu Mingyang, et al. Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113(39): 10890-10895." }, { "name": "MLA", "text": "Darash-Yahana, Merav, et al. \"Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters\" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA., vol. 113, no. 39, 2016, pp. 10890-10895." }, { "name": "APA", "text": "Darash-Yahana Merav, Pozniak Yair, Lu Mingyang, Sohn Yang-Sung, Karmi Ola, Tamir Sagi, ... & Pikarsky Eli (2016). Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(39), 10890-10895." }, { "name": "BibTeX", "text": "@inproceedings{Acemap2371060,\n title=\"Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters\",\n author=\"{Merav Darash-Yahana} and Yair {Pozniak} and Mingyang {Lu} and {Yang-Sung Sohn} and Ola {Karmi} and Sagi {Tamir} and Fang {Bai} and Luhua {Song} and {Patricia A. Jennings} and Eli {Pikarsky} and Tamar {Geiger} and {José N. Onuchic} and Ron {Mittler} and Rachel {Nechushtai}\",\n journal=\"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA\",\n volume=\"113\",\n number=\"39\",\n pages=\"10890--10895\",\n url=\"https://www.acemap.info/paper/2371060\",\n year=\"2016\"\n}" } ] }, { "id": "3794030", "title": "High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells", "abstract": "Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection.", "source_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093305", "doc_type": 4, "year": 2014, "issue": 3, "volume": 9, "first_page": 0, "last_page": 0, "citation_count": 7, "reference_count": 12, "venue": { "id": 2110000215, "name": "PLOS ONE", "abbr": "" }, "author": [ { "id": 1004026063, "name": "Han-Chen Chiu" }, { "id": 1004026064, "name": "Holger Hannemann" }, { "id": 1001266775, "name": "Kate J. Heesom" }, { "id": 1000682457, "name": "David A. Matthews" }, { "id": 1001726644, "name": "Andrew D. Davidson" } ], "field": [ { "id": 2031304391, "name": "Squirrel poxvirus" }, { "id": 2043098908, "name": "Herpes B virus" }, { "id": 2002154009, "name": "Turkey rhinotracheitis virus" }, { "id": 2008362710, "name": "Theiler's disease" }, { "id": 2037114379, "name": "Epithelioma Contagiosum" }, { "id": 2026827718, "name": "Avian nephritis virus" }, { "id": 2020391647, "name": "Mycobacterium marinum" } ], "cite": [ { "name": "GB/T 7714", "text": "Chiu Han-Chen, Hannemann Holger, Heesom Kate J., et al. High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells[J]. PLOS ONE, 2014, 9(3)." }, { "name": "MLA", "text": "Chiu, Han-Chen, et al. \"High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells\" PLOS ONE., vol. 9, no. 3, 2014." }, { "name": "APA", "text": "Chiu Han-Chen, Hannemann Holger, Heesom Kate J., Matthews David A., & Davidson Andrew D. (2014). High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells. PLOS ONE, 9(3)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap3794030,\n title=\"High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells\",\n author=\"{Han-Chen Chiu} and Holger {Hannemann} and {Kate J. Heesom} and {David A. Matthews} and {Andrew D. Davidson}\",\n journal=\"PLOS ONE\",\n volume=\"9\",\n number=\"3\",\n url=\"https://www.acemap.info/paper/3794030\",\n year=\"2014\"\n}" } ] }, { "id": "3762880", "title": "Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell", "abstract": "Cisplatin resistance is one of the major reasons leading to the high death rate of ovarian cancer. Methyl-Capture sequencing (MethylCap-seq), which combines precipitation of methylated DNA by recombinant methyl-CpG binding domain of MBD2 protein with NGS, global and unbiased analysis of global DNA methylation patterns. We applied MethylCap-seq to analyze genome-wide DNA methylation profile of cisplatin sensitive ovarian cancer cell line A2780 and its isogenic derivative resistant line A2780CP. We obtained 21,763,035 raw reads for the drug resistant cell line A2780CP and 18,821,061reads for the sensitive cell line A2780. We identified 1224 hyper-methylated and 1216 hypomethylated DMRs (differentially methylated region) in A2780CP compared to A2780. Our MethylCap-seq data on this ovarian cancer cisplatin resistant model provided a good resource for the research community. We also found that A2780CP, compared to A2780, has lower observed to expected methylated CpG ratios, suggesting a lower global CpG methylation in A2780CP cells. Methylation specific PCR and bisulfite sequencing confirmed hypermethylation of PTK6, PRKCE and BCL2L1 in A2780 compared with A2780CP. Furthermore, treatment with the demethylation reagent 5-aza-dC in A2780 cells demethylated the promoters and restored the expression of PTK6, PRKCE and BCL2L1.", "source_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029450", "doc_type": 4, "year": 2011, "issue": 12, "volume": 6, "first_page": 0, "last_page": 0, "citation_count": 7, "reference_count": 4, "venue": { "id": 2110000215, "name": "PLOS ONE", "abbr": "" }, "author": [ { "id": 1000242113, "name": "Wei Yu" }, { "id": 1003867658, "name": "Chengmeng Jin" }, { "id": 1003879083, "name": "Xiaoyan Lou" }, { "id": 1000224500, "name": "Xu Han" }, { "id": 1001019919, "name": "Lisha Li" }, { "id": 1002186816, "name": "Yinghua He" }, { "id": 1000338234, "name": "Hongyu Zhang" }, { "id": 1003913551, "name": "Kelong Ma" }, { "id": 1001541459, "name": "Jingde Zhu" }, { "id": 1001022344, "name": "Lihua Cheng" }, { "id": 1001232666, "name": "Biaoyang Lin" } ], "field": [ { "id": 2018252668, "name": "Penile cancer" }, { "id": 2017571735, "name": "Migrastatin" }, { "id": 2002788427, "name": "Pyrosequencing" }, { "id": 2047856375, "name": "DNA gyrase" } ], "cite": [ { "name": "GB/T 7714", "text": "Yu Wei, Jin Chengmeng, Lou Xiaoyan, et al. Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell[J]. PLOS ONE, 2011, 6(12)." }, { "name": "MLA", "text": "Yu, Wei, et al. \"Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell\" PLOS ONE., vol. 6, no. 12, 2011." }, { "name": "APA", "text": "Yu Wei, Jin Chengmeng, Lou Xiaoyan, Han Xu, Li Lisha, He Yinghua, ... & Cheng Lihua (2011). Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell. PLOS ONE, 6(12)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap3762880,\n title=\"Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell\",\n author=\"Wei {Yu} and Chengmeng {Jin} and Xiaoyan {Lou} and Xu {Han} and Lisha {Li} and Yinghua {He} and Hongyu {Zhang} and Kelong {Ma} and Jingde {Zhu} and Lihua {Cheng} and Biaoyang {Lin}\",\n journal=\"PLOS ONE\",\n volume=\"6\",\n number=\"12\",\n url=\"https://www.acemap.info/paper/3762880\",\n year=\"2011\"\n}" } ] } ]