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Fabian Koczian, Olga Nagło, Jan Vomacka, Binje Vick, Phil Servatius, Themistoklis Zisis, Britta Hettich, Uli Kazmaier, Stephan A Sieber, Irmela Jeremias, Stefan Zahler, Simone Braig
Combination chemotherapy has proved to be a favorable strategy to treat acute leukemia. However, the introduction of novel compounds remains challenging and is hindered by a lack of understanding their mechanistic interaction with established drugs. In the present study, we demonstrate a highly increased response of various acute leukemia cell lines, drug resistant cells and patient-derived xenograft cells by combining the recently introduced protein disulfide isomerase inhibitor PS89 with cytostatics. In leukemic cells, a proteomics based target fishing approach disclosed that PS89 impacts a whole network of endoplasmic reticulum homeostasis proteins...
October 11, 2018: Haematologica
Zhenhua Wu, Fan Yang, Shan Jiang, Xiaoyu Sun, Jialin Xu
Endoplasmic reticulum (ER) stress is highly associated with liver steatosis. B-cell receptor-associated protein 31 (BAP31) has been reported to be involved in ER homeostasis, and plays key roles in hepatic lipid metabolism in high-fat diet-induced obese mice. However, whether BAP31 modulates hepatic lipid metabolism via regulating ER stress is still uncertain. In this study, wild-type and liver-specific BAP31-depleted mice were administrated with ER stress activator of Tunicamycin, the markers of ER stress, liver steatosis, and the underlying molecular mechanisms were determined...
August 4, 2018: International Journal of Molecular Sciences
Erle Dang, Shuya Yang, Chaojun Song, Dongbo Jiang, Zichao Li, Wei Fan, Yuanjie Sun, Liang Tao, Jing Wang, Tingting Liu, Chunmei Zhang, Boquan Jin, Jian Wang, Kun Yang
Malignant tumors typically undergo an atavistic regression characterized by the overexpression of embryonic genes and proto-oncogenes, including a variety of cancer/testis antigens (CTAs) that are testis-derived and are not expressed or expressed in trace amounts in somatic tissues. Based on this theory, we established a new method to identify unknown CTAs, the spermatogenic cells-specific monoclonal antibody-defined cancer/testis antigen (SADA) method. Using the SADA method, we identified BAP31 as a novel CTA and confirmed that BAP31 expression is associated with progression and metastasis of several cancers, particularly in cervical cancer...
July 18, 2018: Cell Death & Disease
Se-Ri Seo, Hyun Min Lee, Hong Seo Choi, Won-Tae Kim, Eun-Wie Cho, Chun Jeih Ryu
B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein which plays a role as a molecular chaperone for the newly synthesized transmembrane proteins. BAP31 is also an important apoptosis regulator for extrinsic apoptosis induction in the ER membrane. Recent studies have shown that BAP31 is also expressed on the surface of embryonic stem cells. However, the function of cell surface BAP31 (csBAP31) still remains unclarified. In an attempt to search for surface markers on tumorspheres, here, we generated monoclonal antibodies (MAbs) against the sphere cells from the non-small cell lung carcinoma cell (NSCLC) line A549...
2017: PloS One
Jia-Lin Xu, Li-Ya Li, Yan-Qing Wang, Ya-Qi Li, Mu Shan, Shi-Zhuo Sun, Yang Yu, Bing Wang
Conditional knockout mice with targeted disruption of B-cell associated protein (BAP)31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days and markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from WT littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1, and increased hepatic lipid accumulation and HFD-induced liver steatosis...
January 2018: Journal of Lipid Research
Kunwei Niu, Jialin Xu, Yuhua Cao, Yue Hou, Mu Shan, Yanqing Wang, Yang Xu, Mingyi Sun, Bing Wang
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice...
March 23, 2017: Scientific Reports
Won-Tae Kim, Hong Seo Choi, Hyo Jeong Hwang, Han-Sung Jung, Chun Jeih Ryu
[This corrects the article DOI: 10.1371/journal.pone.0130670.].
2017: PloS One
Won-Tae Kim, Saemina Shin, Hyo Jeong Hwang, Min Kyu Kim, Han-Sung Jung, Hwangseo Park, Chun Jeih Ryu
Previously, we showed that B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum (ER) membrane chaperone, is also expressed on the cell surface by two monoclonal antibodies (MAbs) 297-D4 and 144-A8. Both MAbs recognize the same linear epitope on the C-terminal domain of BAP31, although they were independently established. Here, flow cytometric analysis showed that 144-A8 had additional binding properties to some cells, as compared to 297-D4. Quantitative antigen binding assays also showed that 144-A8 had higher antigen binding capacity than 297-D4...
2016: PloS One
Anastasia K Atabekova, Anna V Pankratenko, Svetlana S Makarova, Ekaterina A Lazareva, Robert A Owens, Andrey G Solovyev, Sergey Y Morozov
Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed 'plant BAP-like proteins' (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem...
January 2017: Biochimie
Anna V Pankratenko, Anastasia K Atabekova, Ekaterina A Lazareva, Viktoriia E Baksheeva, Oxana A Zhironkina, Evgeni Yu Zernii, Robert A Owens, Andrey G Solovyev, Sergey Y Morozov
The plant-specific 4/1 protein interacts, both in yeast two-hybrid system and in vitro, and co-localizes in plant cells with plant BAP-like protein, the orthologue of human protein BAP31. In yeast two-hybrid system, we identified a number of Nicotiana benthamiana protein interactors of Nt-4/1, the protein known to affect systemic transport of potato spindle tuber viroid. For one of these interactors, an orthologue of human B-cell receptor-associated protein 31 (BAP31) termed plant BAP-like protein (PBL), the ability to interact with Nt-4/1 was studied in greater detail...
January 2017: Planta
Yuan Jian, Yuling Chen, Chuanying Geng, Nian Liu, Guangzhong Yang, Jinwei Liu, Xin Li, Haiteng Deng, Wenming Chen
Recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) has become a potential therapeutic drug for multiple myeloma (MM). However, the exact targets and resistance mechanisms of rmhTRAIL on MM cells remain to be elucidated. The present study aimed to investigate the target and resistance-related proteins of rmhTRAIL on myeloma cell lines. A TRAIL-sensitive myeloma cell line, RPMI 8226, and a TRAIL-resistance one, U266, were chosen and the differentially expressed proteins between the two cell lines were analyzed prior and subsequent to rmhTRAIL administration by a liquid chromatography-tandem mass spectrometry method...
June 2016: Biomedical Reports
Wayne L Ernst, Kuntala Shome, Christine C Wu, Xiaoyan Gong, Raymond A Frizzell, Meir Aridor
Unesterified cholesterol accumulates in late endosomes in cells expressing the misfolded cystic fibrosis transmembrane conductance regulator (CFTR). CFTR misfolding in the endoplasmic reticulum (ER) or general activation of ER stress led to dynein-mediated clustering of cholesterol-loaded late endosomes at the Golgi region, a process regulated by ER-localized VAMP-associated proteins (VAPs). We hypothesized that VAPs serve as intracellular receptors that couple lipid homeostasis through interactions with two phenylalanines in an acidic track (FFAT) binding signals (found in lipid sorting and sensing proteins, LSS) with proteostasis regulation...
March 4, 2016: Journal of Biological Chemistry
Aleksandra Dabrowska, Jose Luis Venero, Ryota Iwasawa, Mohammed-Khair Hankir, Sunniyat Rahman, Alan Boobis, Nabil Hajji
Due to its role in regulation of mitochondrial function, PGC1α is emerging as an important player in ageing and neurodegenerative disorders. PGC1α exerts its neuroprotective effects by promoting mitochondrial biogenesis (MB) and functioning. However, the precise regulatory role of PGC1α in the control of mitochondrial dynamics (MD) and neurotoxicity is still unknown. Here we elucidate the role of PGC1αin vitro and in vivo in the regulatory context of MB and MD in response to lead (II) acetate as a relevant model of neurotoxicity...
September 2015: Aging
Dae-Hee Lee, Ki Sa Sung, Zong Sheng Guo, William Taehyung Kwon, David L Bartlett, Sang Cheul Oh, Yong Tae Kwon, Yong J Lee
It is well known that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis can be initially triggered by surface death receptors (the extrinsic pathway) and subsequently amplified through mitochondrial dysfunction (the intrinsic pathway). However, little is known about signaling pathways activated by the TRAIL-induced endoplasmic reticulum (ER) stress response. In this study, we report that TRAIL-induced apoptosis is associated with the endoplasmic reticulum (ER) stress response...
May 2016: Journal of Cellular Biochemistry
Reiko Iida, Misuzu Ueki, Toshihiro Yasuda
Human Mpv17-like protein (M-LPH) has been suggested to participate in mitochondrial function. In this study, we investigated the proteins that interact with M-LPH, and identified four: H2A histone family, member X (H2AX), ribosomal protein S14 (RPS14), ribosomal protein S3 (RPS3) and B-cell receptor-associated protein 31 (Bap31). Immunofluorescence and subcellular fractionation studies revealed that M-LPH is localized predominantly in the nucleus, to some extent in a subset of mitochondria, and marginally in the cytosol...
October 2015: Free Radical Biology & Medicine
Won-Tae Kim, Hong Seo Choi, Hyo Jeong Hwang, Han-Sung Jung, Chun Jeih Ryu
When located in the endoplasmic reticulum (ER) membrane, B-cell receptor associated protein 31 (BAP31) is involved in the export of secreted proteins from the ER to the plasma membrane. In a previous study, we generated two monoclonal antibodies (mAbs), 297-D4 and 144-A8, that bound to surface molecules on human embryonic stem cells (hESCs), but not to surface molecules on mouse embryonic stem cells (mESCs). Subsequent studies revealed that the mAbs recognized BAP31 on the surface of hESCs. To investigate the membrane topology of BAP31 on the cell surface, we first examined the epitope specificity of 297-D4 and 144-A8, as well as a polyclonal anti-BAP31 antibody (α-BAP31)...
2015: PloS One
Takamasa Inoue, Annie Dosey, Jeffrey F Herbstman, Madhu Sudhan Ravindran, Georgios Skiniotis, Billy Tsai
UNLABELLED: The nonenveloped polyomavirus (PyV) simian virus 40 (SV40) traffics from the cell surface to the endoplasmic reticulum (ER), where it penetrates the ER membrane to reach the cytosol before mobilizing into the nucleus to cause infection. Prior to ER membrane penetration, ER lumenal factors impart structural rearrangements to the virus, generating a translocation-competent virion capable of crossing the ER membrane. Here we identify ERdj5 as an ER enzyme that reduces SV40's disulfide bonds, a reaction important for its ER membrane transport and infection...
September 2015: Journal of Virology
Ning Tan, Qinyi Liu, Xiaojia Liu, Zhiwei Gong, Yonglian Zeng, Guangdong Pan, Qing Xu, Songqing He
AIMS: The aim of the present study was to investigate the prognostic value of B-cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma (HCC). METHODS AND RESULTS: BAP31 levels were evaluated by immunohistochemistry on tissue microarrays. The integral optical density, representing the expression level of BAP31 in each tissue sample, was calculated with image-pro plus. Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and peritumoral non-cancerous tissues showed that BAP31 expression was significantly higher in HCC tumour tissues (P = 0...
January 2016: Histopathology
Shaojuan Yu, Fuli Wang, Li Fan, Yuying Wei, Haitao Li, Yuanjie Sun, Angang Yang, Boquan Jin, Chaojun Song, Kun Yang
PURPOSE: Malignant melanoma's (MM) incidence is rising faster than that of any other cancer in the US and the overall survival at 5 years is less than 10%. B cell associated protein 31 (BAP31) is overexpressed in most MMs and might be a promising target for immunotherapy of this disease. EXPERIMENTAL DESIGN: Firstly, we investigated the expression profiles of human BAP31 (hBAP31) and mouse BAP31 (mBAP31) in human and mouse normal tissues, respectively. The expression level of hBAP31 in human MMs and mBAP31 in B16 melanoma cells was also analyzed...
2015: Journal of Experimental & Clinical Cancer Research: CR
Yan Li, Neeraj Jain, Suweeraya Limpanawat, Janet To, Esben M Quistgaard, Par Nordlund, Thirumaran Thanabalu, Jaume Torres
The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31...
August 2015: Virology
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