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Jiang Wang, Hongbo You, Jun Qi, Caihong Yang, Ye Ren, Hao Cheng
Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis...
February 9, 2017: Oncotarget
Marta Brunetti, Antonio Agostini, Ben Davidson, Claes G Tropé, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
Juxtaposition of two different genes or gene parts due to chromosomal rearrangement is a well-known neoplasia-associated pathogenetic mechanism. The detection and characterization of such tumorigenic fusions is of great importance both research-wise, diagnostically because they may be specific for distinct tumor entities, and because they may serve as therapeutic targets for antioncogenic drugs that interact directly with the molecular changes responsible for neoplastic transformation.At present, more than 10,000 fusion transcripts have been reported in different types of neoplasia, with one tenth of them being identified in squamous cell carcinomas (SCC) of different locations...
February 7, 2017: Oncotarget
Yue Huang, Hao Li, Lei Wang, Xiaoxia Mao, Genxi Li
In this work, we have successfully designed a smart and flexible signal amplification method based on a newly synthesized hybrid nanocomposite with switchable enzyme activity for specific and sensitive protein detection. The smart hybrid nanocomposite synthesized here is initially loaded with quenched fluorophore and a unique aptamer-inhibited DNA polymerase. It then undergoes target protein-triggered release of the fluorophore and activation of the DNA polymerase, which can thereby promote multiple catalytic reactions and recycled use of the target protein, resulting in the generation of highly amplified signals...
October 4, 2016: ACS Applied Materials & Interfaces
Chia-Lung Tsai, Angel Chao, Shih-Ming Jung, Chi-Neu Tsai, Chiao-Yun Lin, Shun-Hua Chen, Shih-Che Sue, Tzu-Hao Wang, Hsin-Shih Wang, Chyong-Huey Lai
Overexpression of stress-induced phosphoprotein 1 (STIP1) - a co-chaperone of heat shock protein (HSP) 70/HSP90 - and activation of the JAK2-STAT3 pathway occur in several tumors. Combined treatment with a HSP90 inhibitor and a JAK2 inhibitor exert synergistic anti-cancer effects. Here, we show that STIP1 stabilizes JAK2 protein in ovarian and endometrial cancer cells. Knock-down of endogenous STIP1 decreased JAK2 and phospho-STAT3 protein levels. The N-terminal fragment of STIP1 interacts with the N-terminus of JAK2, whereas the C-terminal DP2 domain of STIP1 mediates the interaction with HSP90 and STAT3...
August 2, 2016: Oncotarget
Yu Guo, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by complex interactions between genes and the environment. The expression level of transcription factor regulatory factor X 1 (RFX1) is reduced in T cells from SLE patients. RFX1 can regulate epigenetic modifications of CD70 and CD11a and plays an important role in the development of SLE. However, the mechanisms that mediate reduction of RFX1 in SLE are unclear. Here, we demonstrate that RFX1 protein expression can be tightly regulated by polyubiquitination-mediated proteosomal degradation via STIP1 homology and U-box containing protein 1 (STUB1)...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Andrzej Maciejewski, Valeriy G Ostapchenko, Flavio H Beraldo, Vania F Prado, Marco A M Prado, Wing-Yiu Choy
Soluble oligomers of amyloid-beta peptide (AβO) transmit neurotoxic signals through the cellular prion protein (PrP(C)) in Alzheimer's disease (AD). Secreted stress-inducible phosphoprotein 1 (STIP1), an Hsp70 and Hsp90 cochaperone, inhibits AβO binding to PrP(C) and protects neurons from AβO-induced cell death. Here, we investigated the molecular interactions between AβO and STIP1 binding to PrP(C) and their effect on neuronal cell death. We showed that residues located in a short region of PrP (90-110) mediate AβO binding and we narrowed the major interaction in this site to amino acids 91-100...
July 15, 2016: Biochemical Journal
Marcin Gabryel, Marzena Skrzypczak-Zielinska, Marcin A Kucharski, Ryszard Slomski, Agnieszka Dobrowolska
Glucocorticosteroids (GCs) are used for many years as first-line drugs for the achievement of remission in exacerbations of inflammatory bowel disease (IBD). However, close to 20% of patients are resistant to GCs, and 40% of patients become dependent on GCs. The challenge of today's personalized medicine is the anticipation of the steroid therapy effects even before the initiation of treatment. As several studies show, individually variable response to GCs in population has a genetic background and may depend on gene variability encoding proteins involved in the function and metabolism of GCs...
2016: Scandinavian Journal of Gastroenterology
Khalequz Zaman, Victoria Sawczak, Atiya Zaidi, Maya Butler, Deric Bennett, Paulina Getsy, Maryam Zeinomar, Zivi Greenberg, Michael Forbes, Shagufta Rehman, Vinod Jyothikumar, Kim DeRonde, Abdus Sattar, Laura Smith, Deborah Corey, Adam Straub, Fei Sun, Lisa Palmer, Ammasi Periasamy, Scott Randell, Thomas J Kelley, Stephen J Lewis, Benjamin Gaston
S-nitrosoglutathione (GSNO) reductase regulates novel endogenous S-nitrosothiol signaling pathways, and mice deficient in GSNO reductase are protected from airways hyperreactivity. S-nitrosothiols are present in the airway, and patients with cystic fibrosis (CF) tend to have low S-nitrosothiol levels that may be attributed to upregulation of GSNO reductase activity. The present study demonstrates that 1) GSNO reductase activity is increased in the cystic fibrosis bronchial epithelial (CFBE41o(-)) cells expressing mutant F508del-cystic fibrosis transmembrane regulator (CFTR) compared with the wild-type CFBE41o(-) cells, 2) GSNO reductase expression level is increased in the primary human bronchial epithelial cells expressing mutant F508del-CFTR compared with the wild-type cells, 3) GSNO reductase colocalizes with cochaperone Hsp70/Hsp90 organizing protein (Hop; Stip1) in human airway epithelial cells, 4) GSNO reductase knockdown with siRNA increases the expression and maturation of CFTR and decreases Stip1 expression in human airway epithelial cells, 5) increased levels of GSNO reductase cause a decrease in maturation of CFTR, and 6) a GSNO reductase inhibitor effectively reverses the effects of GSNO reductase on CFTR maturation...
February 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Aline Ketefian, Michelle R Jones, Ronald M Krauss, Yii-Der I Chen, Richard S Legro, Ricardo Azziz, Mark O Goodarzi
OBJECTIVE: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). DESIGN: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters...
February 2016: Fertility and Sterility
Flavio H Beraldo, Anu Thomas, Benjamin Kolisnyk, Pedro H Hirata, Xavier De Jaeger, Amanda C Martyn, Jue Fan, Daniela F Goncalves, Matthew F Cowan, Talal Masood, Vilma R Martins, Robert Gros, Vania F Prado, Marco A M Prado
Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions...
November 2015: Disease Models & Mechanisms
Ana Paula Lappas Gimenez, Larissa Morato Luciani Richter, Mariana Campos Atherino, Breno Castello Branco Beirão, Celso Fávaro, Michele Dietrich Moura Costa, Silvio Marques Zanata, Bettina Malnic, Adriana Frohlich Mercadante
Prion diseases involve the conversion of the endogenous cellular prion protein, PrP(C), into a misfolded infectious isoform, PrP(Sc). Several functions have been attributed to PrP(C), and its role has also been investigated in the olfactory system. PrP(C) is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp(-/-) mice showed impaired behavior in olfactory tests. Given the high PrP(C) expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrP(C)-binding partners...
2015: Prion
Kazuhiro Tokuda, Yasuhiro Kuramitsu, Baron Byron, Takao Kitagawa, Nobuko Tokuda, Daiki Kobayashi, Megumi Nagayama, Norie Araki, Koh-Hei Sonoda, Kazuyuki Nakamura
Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage...
August 7, 2015: Biochemical and Biophysical Research Communications
Chang-Peng Xu, Xue Li, Yan-Jun Hu, Zhuang Cui, Lei Wang, Liang Liang, Yi-Lin Zhou, Ya-Jun Yang, Bin Yu
UNLABELLED: TNF-α, one of the most potent pro-inflammatory cytokines, plays a critical role in inhibition of osteoblast differentiation and bone regeneration in persistent inflammatory microenvironment. To explore the mechanism, quantitative proteomics based on iTRAQ and MRM was employed. The results showed 6 proteins involved in BMP-2 induced osteoblast differentiation inhibition by TNF-α: Periostin, Protein S100-A4, ATPase inhibitor, Cytochrome b5, SERCA3, and ELP2. The altered proteins were involved in molecular transport, tissue development, energy metabolism, and inflammation...
January 30, 2015: Journal of Proteomics
Yanwei Wang, Shaohua Jin, Ning Li, Juan Liu, Hui Shi, Yan Li
Stress-inducible protein 1 (Stip1) is one of the well-studied co-chaperones, although limited researches have been conducted in testis and epididymis. Here we found that Stip1 was ubiquitously expressed in various human tissues, including the testis and epididymis. In human testis and epididymis, Stip1 was localized in the cytoplasm of diverse cell types. Stip1 showed a developmentally-regulated manner and it was up-regulated after heat shock in rat testis and epididymis. However, the expression of Stip1 was significantly down-regulated in the testis, with tremendous histomorphological changes under oxidative stress...
January 1, 2015: Gene
Ling Lu, Qin Lan, Zhiyuan Li, Xiaohui Zhou, Jian Gu, Qiang Li, Julie Wang, Maogen Chen, Ya Liu, Yi Shen, David D Brand, Bernhard Ryffel, David A Horwitz, Francisco P Quismorio, Zhongmin Liu, Bin Li, Nancy J Olsen, Song Guo Zheng
Recent studies have demonstrated that thymus-derived naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize atRA stabilizes human natural Tregs (nTregs) under inflammatory conditions. atRA prevents human nTregs from converting to Th1 and/or Th17 cells and sustains their Foxp3 expression and suppressive function in vitro or in vivo following encounters with IL-1 and IL-6...
August 19, 2014: Proceedings of the National Academy of Sciences of the United States of America
Hideki Maejima, Ryo Nagashio, Kengo Yanagita, Yuko Hamada, Yasuyuki Amoh, Yuichi Sato, Kensei Katsuoka
To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB). Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17), annexin A1 (ANXA1), and stress-induced phophoprotein-1 (STIP1), which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls...
2014: PloS One
Y Izuhara, H Matsumoto, Y Kanemitsu, K Izuhara, Y Tohda, T Horiguchi, H Kita, K Kuwabara, K Tomii, K Otsuka, M Fujimura, N Ohkura, K Tomita, A Yokoyama, H Ohnishi, Y Nakano, T Oguma, S Hozawa, T Nagasaki, I Ito, T Oguma, H Inoue, T Tajiri, T Iwata, J Ono, S Ohta, M Tamari, T Hirota, T Yokoyama, A Niimi, M Mishima
BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation...
May 2014: Allergy
Dimitri Van Simaeys, Diane Turek, Carole Champanhac, Julia Vaizer, Kwame Sefah, Jing Zhen, Rebecca Sutphen, Weihong Tan
In this paper, we describe the elucidation of the target of an aptamer against ovarian cancer previously obtained by cell-SELEX (SELEX = systematic evolution of ligands by exponential enrichment). The target's identity, stress-induced phosphoprotein 1 (STIP1), was determined by mass spectrometry and validated by flow cytometry, using siRNA silencing and protein blotting. Initial oncologic studies show that the aptamer inhibits cell invasion, indicating that STIP1, which is currently under investigation as a potential biomarker for ovarian cancer, plays a critical role in this process...
May 6, 2014: Analytical Chemistry
Hanbyoul Cho, Sunghoon Kim, Ha-Yeon Shin, Eun Joo Chung, Haruhisa Kitano, Jae Hyon Park, Lucienne Park, Joon-Yong Chung, Stephen M Hewitt, Jae-Hoon Kim
Stress-induced phosphoprotein1 (STIP1) is a candidate biomarker in epithelial ovarian cancer (EOC). In this study, we investigated in detail the expression of STIP1, as well as its functions, in EOC. STIP1 expression was assessed by immunohistochemistry (IHC) and the results were compared with clinicopathologic factors, including survival data. The effects of STIP1 gene silencing via small interfering RNA (siRNA) were examined in EOC cells and a xenograft model. The expression of STIP1 protein in EOC was significantly higher than in the other study groups (P < 0...
April 2014: Genes, Chromosomes & Cancer
Jun-Hu Chen, Ting Zhang, Chuan Ju, Bin Xu, Yan Lu, Xiao-Jin Mo, Shen-Bo Chen, Yan-Ting Fan, Wei Hu, Xiao-Nong Zhou
UNLABELLED: Schistosomiasis remains one of the major neglected tropical diseases (NTDs) causing morbidity of humans residing in the tropical countries. Much effort has been devoted to the development of vaccines, since it is recognized that vaccines can be served as an important supplementary component alongside chemotherapy for the future control and elimination of schistosomiasis. To accelerate digging new potential target antigens, it is essential to extensively and intensively search immunogenic proteins in a high-throughput manner using proteomics-microarray techniques...
February 26, 2014: Journal of Proteomics
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