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https://www.readbyqxmd.com/read/28715732/proteasome-inhibitor-induced-cleavage-of-hsp90-is-mediated-by-ros-generation-and-caspase-10-activation-in-human-leukemic-cells
#1
Sangkyu Park, Jeong-A Park, Hwanmin Yoo, Han-Bum Park, Younghee Lee
Heat shock protein 90 (HSP90) is a molecular chaperone that supports the stability of client proteins. The proteasome is one of the targets for cancer therapy, and studies are underway to use proteasome inhibitors as anti-cancer drugs. In this study, we found that HSP90 was cleaved to a 55kDa protein after treatment with proteasome inhibitors including MG132 in leukemia cells but was not cleaved in other tissue-derived cells. HSP90 has two major isoforms (HSP90α and HSP90β), and both were cleaved by MG132 treatment...
July 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28688199/differential-expression-of-park2-splice-isoforms-in-an-in-vitro-model-of-dopaminergic-like-neurons-exposed-to-toxic-insults-mimicking-parkinson-s-disease
#2
Valentina La Cognata, Grazia Maugeri, Agata Grazia D'Amico, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Mutations in PARK2 (or parkin) are responsible for 50% of cases of autosomal-recessive juvenile-onset Parkinson's disease (PD). To date, 21 alternative splice variants of the human gene have been cloned. Yet most studies have focused on the full-length protein, whereas the spectrum of the parkin isoforms expressed in PD has never been investigated. In this study, the role of parkin proteins in PD neurodegeneration was explored for the first time by analyzing their expression profile in an in vitro model of PD...
July 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28681940/transcriptional-regulation-of-runx2-by-hsp90-controls-osteosarcoma-apoptosis-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#3
Gui-Hong Liang, Ning Liu, Ming-Tang He, Jie Yang, Zu-Jian Liang, Xue-Juan Gao, Ali Hasan Rahhal, Qing-Yu He, Huan-Tian Zhang, Zhen-Gang Zha
Osteosarcoma (OS) is the most malignant primary bone tumor in children and adolescents with limited treatment options and poor prognosis. Recently, aberrant expression of Runx2 has been found in OS, thereby contributing to the development and progression of OS. However, the upstream signaling molecules that regulate its expression in OS remain largely unknown. In the present study, we first confirmed that the inhibition of HSP90 with 17-AAG caused significant apoptosis of OS cells via a caspase-3-dependent mechanism, and that inhibition or knockdown of HSP90 by 17-AAG or siRNAs significantly suppressed mRNA and protein expression of Runx2...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28676568/extended-c-termini-of-cpc-like-myb-proteins-confer-functional-diversity-in-arabidopsis-epidermal-cell-differentiation
#4
Rumi Tominaga-Wada, Takuji Wada
The CAPRICE (CPC) gene encodes a R3-type MYB transcription factor that promotes differentiation of root hair cells in Arabidopsis thaliana Here, we have compared the functions of five CPC-homologous genes for epidermal cell differentiation using CPC promoter-driven transgenic plants. Our results show that TRIPTYCHON (TRY) and ENHANCER OF TRY AND CPC2 (ETC2) were less effective in root hair cell differentiation and were unstable in root epidermal cells when compared with CPC, ETC1 or CPC LIKE MYB3 (CPL3). The deletion of the extended C-terminal domain of TRY and ETC2 enhanced protein stability and conferred the ability to induce root hair cell differentiation on them...
July 1, 2017: Development
https://www.readbyqxmd.com/read/28674081/mg132-induced-progerin-clearance-is-mediated-by-autophagy-activation-and-splicing-regulation
#5
Karim Harhouri, Claire Navarro, Danielle Depetris, Marie-Geneviève Mattei, Xavier Nissan, Pierre Cau, Annachiara De Sandre-Giovannoli, Nicolas Lévy
Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature and accelerated aging disease caused by a de novo point mutation in LMNA encoding A-type lamins. Progerin, a truncated and toxic prelamin A issued from aberrant splicing, accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. We show that progerin is sequestered into abnormally shaped promyelocytic nuclear bodies, identified as novel biomarkers in late passage HGPS cell lines...
July 3, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28673005/celastrol-inhibits-migration-and-invasion-through-blocking-the-nf-%C3%AE%C2%BAb-pathway-in-ovarian-cancer-cells
#6
Zhongye Wang, Zhenyuan Zhai, Xiulan Du
Metastatic ovarian cancer is a major clinical challenge with poor prognosis and high mortality. Celastrol is a natural compound that has exhibits antiproliferative activity; however, its effects on metastasis-related phenotypes in ovarian cancer models are unclear. In the current study, the anti-invasive activities and associated signaling pathways of celastrol were determined in ovarian cancer cells. Cell proliferation was tested by MTT assay. Cell migration was detected by wound healing and Transwell assays, while cell invasion was detected by a Matrigel-coated Transwell method...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28669733/bcl11b-is-frequently-downregulated-in-htlv-1-infected-t-cells-through-tax-mediated-proteasomal-degradation
#7
Happy Kurnia Permatasari, Shingo Nakahata, Tomonaga Ichikawa, Kazuhiro Morishita
Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia-lymphoma (ATLL). The HTLV-1-encoded protein Tax plays important roles in the proliferation of HTLV-1-infected T-cells by affecting cellular proteins. In this study, we showed that Tax transcriptionally and post-transcriptionally downregulates the expression of the tumor suppressor gene B-cell leukemia/lymphoma 11B (BCL11B), which encodes a lymphoid-related transcription factor. BCL11B expression was downregulated in HTLV-1-infected T-cell lines at the mRNA and protein levels, and forced expression of BCL11B suppressed the proliferation of these cells...
June 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28668976/abscisic-acid-regulated-protein-degradation-causes-osmotic-stress-induced-accumulation-of-branched-chain-amino-acids-in-arabidopsis-thaliana
#8
Tengfang Huang, Georg Jander
Whereas proline accumulates through de novo biosynthesis in plants subjected to osmotic stress, leucine, isoleucine, and valine accumulation in drought-stressed Arabidopsis thaliana is caused by abscisic acid-regulated protein degradation. In response to several kinds of abiotic stress, plants greatly increase their accumulation of free amino acids. Although stress-induced proline increases have been studied the most extensively, the fold-increase of other amino acids, in particular branched-chain amino acids (BCAAs; leucine, isoleucine, and valine), is often higher than that of proline...
July 1, 2017: Planta
https://www.readbyqxmd.com/read/28651835/andrographolide-reduced-vegfa-expression-in-hepatoma-cancer-cells-by-inactivating-hif-1%C3%AE-the-involvement-of-jnk-and-mta1-hdca
#9
Liang Shi, Guoqing Zhang, Zhiyong Zheng, Bin Lu, Lili Ji
Andrographolide (Andro) is the main active compound in medicinal herb Andrographis paniculata Nees (Acanthaceae). Vascular endothelial growth factor A (VEGFA), a key pro-angiogenic factor, contributes greatly to tumor growth. The purpose of this study is to observe the inhibition of Andro on VEGFA expression in hepatoma cancer cells and its engaged mechanism. Andro decreased mRNA and protein expression of VEGFA in hepatoma Hep3B and HepG2 cells. Andro also decreased hypoxia-inducible factor 1-alpha (HIF-1α) protein expression and its subsequent nuclear translocation...
June 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28637969/development-of-a-patient-derived-induced-pluripotent-stem-cell-model-for-the-investigation-of-scn5a-d1275n-related-cardiac-sodium-channelopathy
#10
Mamoru Hayano, Takeru Makiyama, Tsukasa Kamakura, Hiroshi Watanabe, Kenichi Sasaki, Shunsuke Funakoshi, Yimin Wuriyanghai, Suguru Nishiuchi, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Fumika Yokoi, Jiarong Chen, Osamu Baba, Takahiro Horie, Kazuhisa Chonabayashi, Seiko Ohno, Futoshi Toyoda, Yoshinori Yoshida, Koh Ono, Minoru Horie, Takeshi Kimura
BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type...
June 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28637474/arsenic-trioxide-inhibits-ebv-reactivation-and-promotes-cell-death-in-ebv-positive-lymphoma-cells
#11
Qinyan Yin, Mark Sides, Christopher H Parsons, Erik K Flemington, Joseph A Lasky
BACKGROUND: Epstein-Barr Virus (EBV) is associated with hematopoietic malignancies, such as Burkitt's lymphoma, post-transplantation lymphoproliferative disorder, and diffuse large B-cell lymphoma. The current approach for EBV-associated lymphoma involves chemotherapy to eradicate cancer cells, however, normal cells may be injured and organ dysfunction may occur with currently employed regimens. This research is focused on employing arsenic trioxide (ATO) as EBV-specific cancer therapy takes advantage of the fact the EBV resides within the malignant cells...
June 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28626006/atairp2-e3-ligase-affects-aba-and-high-salinity-responses-by-stimulating-its-atp1-sdirip1-substrate-turnover
#12
Tae Rin Oh, Jong Hum Kim, Seok Keun Cho, Moon Young Ryu, Seong Wook Yang, Woo Taek Kim
AtAIRP2 is a cytosolic RING-type E3 ubiquitin (Ub) ligase that positively regulates an ABA response in Arabidopsis (Arabidopsis thaliana). Yeast two-hybrid screening using AtAIRP2 as bait identified ATP1 (AtAIRP2 Target Protein 1) as a substrate of AtAIRP2. ATP1 was found to be identical to SDIRIP1, which was recently reported to be a negative factor in ABA signaling and a target protein of the RING E3 ligase SDIR1. ATP1 was accordingly renamed ATP1/SDIRIP1. A specific interaction between AtAIRP2 and ATP1/SDIRIP1 and ubiquitination of ATP1/SDIRIP1 by AtAIRP2 were demonstrated in vitro and in planta...
June 16, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#13
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28613983/azithromycin-attenuates-myofibroblast-differentiation-and-lung-fibrosis-development-through-proteasomal-degradation-of-nox4
#14
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor beta) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28599312/cullin-3spop-ubiquitin-e3-ligase-promotes-the-poly-ubiquitination-and-degradation-of-hdac6
#15
Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Fei Wu, Jianping Guo, Deliang Liu, Brian J North, Jirong Huo, Jinfang Zhang
The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28593149/effects-of-a-proteasome-inhibitor-on-cardiomyocytes-in-a-pressure-overload-hypertrophy-rat-model-an-animal-study
#16
In-Sub Kim, Won-Min Jo
BACKGROUND: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model...
June 2017: Korean Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28588709/growth-inhibition-of-human-breast-carcinoma-cells-by-overexpression-of-regulator-of-g-protein-signaling-4
#17
Hyun-Jung Park, Seung-Hyun Kim, Dong-Oh Moon
Breast cancer remains the second largest cause of mortality in women with cancer and does not respond well to conventional therapies. Regulator of G-protein signaling 4 (RGS4) is a GTPase-activating protein of the heterotrimeric Gq and Gi proteins. Altered levels of RGS4 are reportedly linked with several human diseases, including cancer. The present study investigated whether overexpression of RGS4 inhibited the growth of human breast cancer cells. Protein expression was investigated by western blot analysis...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28580641/melatonin-reduces-endoplasmic-reticulum-stress-and-corneal-dystrophy-associated-tgfbip-through-activation-of-endoplasmic-reticulum-associated-protein-degradation
#18
Seung-Il Choi, Eunhee Lee, Begum Akuzum, Jang Bin Jeong, Yong-Sun Maeng, Tae-Im Kim, Eung Kweon Kim
Endoplasmic reticulum (ER) stress is emerging as a factor for the pathogenesis of granular corneal dystrophy type 2 (GCD2). This study was designed to investigate the molecular mechanisms underlying the protective effects of melatonin on ER stress in GCD2. Our results showed that GCD2 corneal fibroblasts were more susceptible to ER stress-induced death than were wild-type cells. Melatonin significantly inhibited GCD2 corneal cell death, caspase-3 activation, and poly (ADP-ribose) polymerase 1 cleavage caused by the ER stress inducer, tunicamycin...
June 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#19
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28566374/the-sat-protein-of-porcine-parvovirus-accelerates-viral-spreading-through-irreversible-er-stress-induction
#20
István Mészáros, Renáta Tóth, Ferenc Olasz, Peter Tijssen, Zoltán Zádori
The SAT protein of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER) and SAT deletion induces "slow spreading" phenotype. The in vitro comparison of the wild type Kresse strain and its SAT(-) knockout mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT(-) virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences were detected in the quantity and the localization of CHOP, suggesting a role of SATp in the induction of irreversible ER stress in infected cells...
May 31, 2017: Journal of Virology
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