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https://www.readbyqxmd.com/read/28986450/stap-2-promotes-prostate-cancer-growth-by-enhancing-egfr-stabilization
#1
Yuichi Kitai, Masashi Iwakami, Kodai Saitoh, Sumihito Togi, Serina Isayama, Yuichi Sekine, Ryuta Muromoto, Jun-Ichi Kashiwakura, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda
Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through upregulation of EGFR signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28972304/dr5-cbl-b-c-cbl-traf2-complex-inhibits-trail-induced-apoptosis-by-promoting-traf2-mediated-polyubiquitination-of-caspase-8-in-gastric-cancer-cells
#2
Ling Xu, Ye Zhang, Xiujuan Qu, Xiaofang Che, Tianshu Guo, Ce Li, Rui Ma, Yibo Fan, Yanju Ma, Kezuo Hou, Danni Li, Xuejun Hu, Bofang Liu, Ruoxi Yu, Hongfei Yan, Jing Gong, Yunpeng Liu
Ubiquitination of caspase-8 regulates TRAIL sensitivity in cancer cell, and the preligand assembly complex plays a role in caspase-8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL-triggered apoptosis is unclear. In the present study, DR5, Cbl-b/c-Cbl, and TRAF2 formed a complex in TRAIL-resistant gastric cancer cells, and Cbl-b and c-Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase-8 translocation into the DR5-Cbl-b/c-Cbl-TRAF2 complex to interact with TRAF2, which then mediated the K48-linked polyubiquitination of caspase-8...
October 3, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28846104/berberine-binds-rxr%C3%AE-to-suppress-%C3%AE-catenin-signaling-in-colon-cancer-cells
#3
H Ruan, Y Y Zhan, J Hou, B Xu, B Chen, Y Tian, D Wu, Y Zhao, Y Zhang, X Chen, P Mi, L Zhang, S Zhang, X Wang, H Cao, W Zhang, H Wang, H Li, Y Su, X K Zhang, T Hu
Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#4
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28605050/the-abl-1-kinase-is-dispensable-for-nk-cell-inhibitory-signalling-and-is-not-involved-in-murine-nk-cell-education
#5
S Ganesan, T T Luu, B J Chambers, S Meinke, P Brodin, E Vivier, D M Wetzel, A J Koleske, N Kadri, P Höglund
Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires...
September 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28541302/the-long-noncoding-rna-lnc-egfr-stimulates-t-regulatory-cells-differentiation-thus-promoting-hepatocellular-carcinoma-immune-evasion
#6
Runqiu Jiang, Junwei Tang, Yun Chen, Lei Deng, Jie Ji, Yu Xie, Ke Wang, Wei Jia, Wen-Ming Chu, Beicheng Sun
Long noncoding RNAs play a pivotal role in T-helper cell development but little is known about their roles in Treg differentiation and functions during the progression of hepatocellular carcinoma (HCC). Here, we show that lnc-epidermal growth factor receptor (EGFR) upregulation in Tregs correlates positively with the tumour size and expression of EGFR/Foxp3, but negatively with IFN-γ expression in patients and xenografted mouse models. Lnc-EGFR stimulates Treg differentiation, suppresses CTL activity and promotes HCC growth in an EGFR-dependent manner...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28415719/endosomal-sorting-and-c-cbl-targeting-of-paxillin-to-autophagosomes-regulate-cell-matrix-adhesion-turnover-in-human-breast-cancer-cells
#7
Chia-Hao Chang, Krikor Bijian, Dinghong Qiu, Jie Su, Amine Saad, Michael S Dahabieh, Wilson H Miller, Moulay A Alaoui-Jamali
Post-translational mechanisms regulating cell-matrix adhesion turnover during cell locomotion are not fully elucidated. In this study, we uncovered an essential role of Y118 site-specific tyrosine phosphorylation of paxillin, an adapter protein of focal adhesion complexes, in paxillin recruitment to autophagosomes to trigger turnover of peripheral focal adhesions in human breast cancer cells. We demonstrate that the Rab-7 GTPase is a key upstream regulator of late endosomal sorting of tyrosine118-phosphorylated paxillin, which is subsequently recruited to autophagosomes via the cargo receptor c-Cbl...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28287082/e3-ligase-fbxw7-is-critical-for-rig-i-stabilization-during-antiviral-responses
#8
Yinjing Song, Lihua Lai, Zhenlu Chong, Jia He, Yuanyuan Zhang, Yue Xue, Yiwei Xie, Songchang Chen, Ping Dong, Luoquan Chen, Zhimin Chen, Feng Dai, Xiaopeng Wan, Peng Xiao, Xuetao Cao, Yang Liu, Qingqing Wang
Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28245373/-role-and-mechanism-of-the-interaction-of-bcr-abl-with-e3-ligase-c-cbl-in-targeting-therapy-of-chronic-myelogenous-leukemia
#9
Jian-Hua Mao, Qiu-Hua Huang, Ping Liu, Cheng Luo, Xiao-Dong Xi
OBJECTIVE: To explore the interaction domains between BCR-ABL and E3 liagase c-CBL, so as to reveal the structure-basis for the arsenic to treat chronic myelogenous leukemia(CML). METHODS: The interactional interface of BCR-ABL and c-CBL was simulated and analyzed according to the available structure model. Based on the structural information, the WT and mutant Migr1-BCR-ABL-GFP (ΔSH2,ΔTyrKC,ΔSH2/TyrKC (S/H) and pFlag-c-CBL (ΔRF) were constructed and co-transfected into the 293T and HeLa cells...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27903975/cortactin-promotes-colorectal-cancer-cell-proliferation-by-activating-the-egfr-mapk-pathway
#10
Xiaojian Zhang, Kun Liu, Tao Zhang, Zhenlei Wang, Xuan Qin, Xiaoqian Jing, Haoxuan Wu, Xiaopin Ji, Yonggang He, Ren Zhao
Cortactin (CTTN) is overexpressed in various tumors, including head and neck squamous cell carcinoma and colorectal cancer (CRC), and can serve as a biomarker of cancer metastasis. We observed that CTTN promotes cancer cell proliferation in vitro and increases CRC tumor xenograft growth in vivo. CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#11
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27805921/c-cbl-e3-ubiquitin-ligase-expression-increases-across-the-spectrum-of-benign-and-malignant-t-cell-skin-diseases
#12
Katrin A Salva, Margo J Reeder, Rita Lloyd, Gary S Wood
Prolonged survival of lesional T cells plays a central role in the pathogenesis of T-cell-mediated dermatoses. We have recently shown that the ubiquitin ligase c-CBL is highly expressed in cutaneous T-cell lymphoma (CTCL) and that its knockdown increases activation-induced cell death, a key pathway for T-cell apoptosis. Here, we extend our work on c-CBL expression in malignant T cells to their nonneoplastic counterparts in benign inflammatory dermatoses. Immunohistochemical staining with anti-c-CBL antibody was performed on lesional biopsies from a total of 65 patients with atopic dermatitis, allergic contact dermatitis, pityriasis rosea, psoriasis vulgaris, lichen planus, mycosis fungoides (MF)/Sézary syndrome (SS) as well as on tonsil tissue from 5 individuals and on 5 human CTCL cell lines...
October 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27764233/escrt-i-protein-tsg101-plays-a-role-in-the-post-macropinocytic-trafficking-and-infection-of-endothelial-cells-by-kaposi-s-sarcoma-associated-herpesvirus
#13
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27708243/jwa-down-regulates-her2-expression-via-c-cbl-and-induces-lapatinib-resistance-in-human-gastric-cancer-cells
#14
Ling Ma, Weiyou Zhu, Qiang Wang, Fengming Yang, Jing Qian, Tongpeng Xu, Shouyu Wang, Jianwei Zhou, Yongqian Shu
Human epidermal growth factor receptor 2 (HER2) targeted therapy is currently considered as the standard treatment for HER2-positive advanced gastric cancer (GC). However, unsatisfactory results of recent phase III clinical trials involving lapatinib suggested biomarkers for selection of patients. The aim of this study was to identify JWA as a biomarker for lapatinib resistance in GC cells and elucidate the underlying mechanisms. Lapatinib was effective to the intrinsic cisplatin-resistant GC cells. JWA activation conferred lapatinib unresponsiveness, but reversed cisplatin resistance in GC cells...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27693578/the-e3-ubiquitin-ligase-c-cbl-mediates-integrin-%C3%AE-1-ubiquitination-during-dilated-cardiomyopathy
#15
Nan Yang, Fang Yu, Genze Shao, Yi Fu, Wei Kong
Dilated cardiomyopathy (DCM) is characterized by dilatation of the ventricular chambers and impaired myocardial contractility. The results of our previous study indicated that a deficiency in matricellular cartilage oligomeric matrix protein (COMP) led to spontaneous and progressive DCM in mice via the ubiquitination/degradation of integrin β1. However, the specific ubiquitin enzyme involved in degradation of integrin β1 and the pathogenesis of DCM remain elusive. We first compared gene expression profiles in hearts from 3-month-old wild type and COMP(-/-) mice using microarray analysis...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27661103/c-cbl-mediates-the-degradation-of-tumorigenic-nuclear-%C3%AE-catenin-contributing-to-the-heterogeneity-in-wnt-activity-in-colorectal-tumors
#16
Moshe Shashar, Jamaica Siwak, Umit Tapan, Shin Yin Lee, Rosana D Meyer, Paige Parrack, Josenia Tan, Fatemeh Khatami, Jean Francis, Qing Zhao, Kevan Hartshorn, Vijaya B Kolachalama, Nader Rahimi, Vipul Chitalia
Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear β-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear β-catenin in human CRC. Herein, we investigated the effect of Casitas B-lineage lymphoma (c-Cbl) on nuclear β-catenin, which is an oncoprotein upregulated in CRC due to loss-of-function APC or gain-of-function CTNNB1 mutations...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27612423/differential-protein-stability-of-egfr-mutants-determines-responsiveness-to-tyrosine-kinase-inhibitors
#17
Paramita Ray, Yee Sun Tan, Vishal Somnay, Ranjit Mehta, Merna Sitto, Aarif Ahsan, Shyam Nyati, John P Naughton, Alexander Bridges, Lili Zhao, Alnawaz Rehemtulla, Theodore S Lawrence, Dipankar Ray, Mukesh K Nyati
Non-small cell lung cancer (NSCLC) patients carrying specific EGFR kinase activating mutations (L858R, delE746-A750) respond well to tyrosine kinase inhibitors (TKIs). However, drug resistance develops within a year. In about 50% of such patients, acquired drug resistance is attributed to the enrichment of a constitutively active point mutation within the EGFR kinase domain (T790M). To date, differential drug-binding and altered ATP affinities by EGFR mutants have been shown to be responsible for differential TKI response...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27609087/casitas-b-lineage-lymphoma-linker-helix-mutations-found-in-myeloproliferative-neoplasms-affect-conformation
#18
Lori Buetow, Giancarlo Tria, Syed Feroj Ahmed, Andreas Hock, Hao Dou, Gary J Sibbet, Dmitri I Svergun, Danny T Huang
BACKGROUND: Casitas B-lineage lymphoma (Cbl or c-Cbl) is a RING ubiquitin ligase that negatively regulates protein tyrosine kinase (PTK) signalling. Phosphorylation of a conserved residue (Tyr371) on the linker helix region (LHR) between the substrate-binding and RING domains is required to ubiquitinate PTKs, thereby flagging them for degradation. This conserved Tyr is a mutational hotspot in myeloproliferative neoplasms. Previous studies have revealed that select point mutations in Tyr371 can potentiate transformation in cells and mice but not all possible mutations do so...
2016: BMC Biology
https://www.readbyqxmd.com/read/27503123/c-cbl-mediated-ubiquitination-of-irf3-negatively-regulates-ifn-%C3%AE-production-and-cellular-antiviral-response
#19
Xibao Zhao, Huihui Zhu, Juan Yu, Hongrui Li, Jiafeng Ge, Weilin Chen
Induction of type I interferon is a fundamental cellular response to viral infection. Interferon regulatory factor 3 (IRF3) plays an essential role in Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) mediated induction of type I interferon and host antiviral responses. However, posttranslational regulation of IRF3 remains to be fully understood. In this study, we identified E3 ubiquitin ligase Casitas B-lineage lymphoma (c-Cbl) as a negative regulator for IRF3 protein stability and IFN-β signal pathway...
November 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27472394/c-cbl-regulates-melanoma-proliferation-migration-invasion-and-the-fak-src-grb2-nexus
#20
Minakshi Nihal, Gary S Wood
Melanoma is one of the most aggressive and lethal forms of skin cancer. Despite recent improvements in targeted therapies, many patients with advanced disease fail to achieve lasting tumor regression. Therefore, it is important to develop novel druggable targets that can be exploited to improve clinical outcome. Here, we studied the role of Casitas B-lineage lymphoma (c-CBL), an E3 ubiquitin ligase, in human melanoma. Employing quantitative real-time PCR and Western blot analysis in a panel of human melanoma cell lines (A375, G361, Hs-294T, SK-Mel-2, SK-Mel-28 and 451Lu), we found that c-CBL is strongly expressed in human melanoma cells at the mRNA and protein levels...
August 16, 2016: Oncotarget
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