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https://www.readbyqxmd.com/read/29899407/the-e3-ligase-c-cbl-inhibits-cancer-cell-migration-by-neddylating-the-proto-oncogene-c-src
#1
Gun-Woo Lee, Jun Bum Park, Sung Yeon Park, Jieun Seo, Seung-Hyun Shin, Jong-Wan Park, Sang Jung Kim, Masatoshi Watanabe, Yang-Sook Chun
Neddylation is a cellular process that covalently conjugates substrate proteins with the small ubiquitin-like molecule NEDD8. As neddylation is required for fast turnover of proteins in proliferating cancer cells, the neddylation process is currently regarded as a potential target for cancer therapy. However, little is known about the role of neddylation in cancer invasion and metastasis. Unexpectedly, we here found that the neddylation blockade stimulates migration of lung cancer and glioblastoma cells. Mechanistically, C-CBL acts as the E3 ligase for neddylation of the proto-oncogene c-Src...
June 13, 2018: Oncogene
https://www.readbyqxmd.com/read/29891719/regulation-of-a-distinct-activated-ripk1-intermediate-bridging-complex-i-and-complex-ii-in-tnf%C3%AE-mediated-apoptosis
#2
Palak Amin, Marcus Florez, Ayaz Najafov, Heling Pan, Jiefei Geng, Dimitry Ofengeim, Slawomir A Dziedzic, Huibing Wang, Vica Jean Barrett, Yasushi Ito, Matthew J LaVoie, Junying Yuan
Stimulation of cells with TNFα can promote distinct cell death pathways, including RIPK1-independent apoptosis, necroptosis, and RIPK1-dependent apoptosis (RDA)-the latter of which we still know little about. Here we show that RDA involves the rapid formation of a distinct detergent-insoluble, highly ubiquitinated, and activated RIPK1 pool, termed "iuRIPK1." iuRIPK1 forms after RIPK1 activation in TNF-receptor-associated complex I, and before cytosolic complex II formation and caspase activation...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29876933/activation-of-met-signaling-by-hdac6-offers-a-rationale-for-a-novel-ricolinostat-and-crizotinib-combinatorial-therapeutic-strategy-in-diffuse-large-b-cell-lymphoma
#3
Zebing Liu, Ying Cai, Yu Yang, Anqi Li, Rui Bi, Lisha Wang, Xiaohan Shen, Weige Wang, Yijun Jia, Baohua Yu, Bing Cao, Wenli Cui, Ping Wei, Xiaoyan Zhou
Some histone deacetylases (HDACs) promote tumor cell growth and pan- or selective HDAC inhibitors are active in some cancers, however, the pivotal HDAC enzyme and its functions in human diffuse large B-cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo...
June 7, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29720121/c-cbl-reverses-her2-mediated-tamoxifen-resistance-in-human-breast-cancer-cells
#4
Wei Li, Ling Xu, Xiaofang Che, Haizhou Li, Ye Zhang, Na Song, Ti Wen, Kezuo Hou, Yi Yang, Lu Zhou, Xing Xin, Lu Xu, Xue Zeng, Sha Shi, Yunpeng Liu, Xiujuan Qu, Yuee Teng
BACKGROUND: Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. METHODS: MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29665313/refinement-of-the-endogenous-epitope-tagging-technology-allows-the-identification-of-a-novel-nras-binding-partner-in-melanoma
#5
Michal Alon, Rafi Emmanuel, Nouar Qutob, Anna Bakhman, Victoria Peshti, Alexandra Brodezki, David Bassan, Mickey Kosloff, Yardena Samuels
The NRAS oncoprotein is highly mutated in melanoma. However, to date, no comprehensive proteomic study has been reported for NRAS. Here, we utilized the endogenous epitope tagging (EET) approach for the identification of novel NRAS binding partners. Using EET, an epitope tag is added to the endogenously expressed protein, via modification of its genomic coding sequence. Existing EET systems are not robust, suffer from high background, and are labor-intensive. To this end, we present a polyadenylation signal-trap construct for N'-tagging that generates a polycistronic mRNA with the gene of interest...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29629558/%C3%AE-catenin-increases-the-stability-of-egfr-by-decreasing-c-cbl-interaction-and-enhances-egfr-erk1-2-signaling-in-prostate-cancer
#6
Nensi Shrestha, Hridaya Shrestha, Taeyong Ryu, Hangun Kim, Shishli Simkhada, Young-Chang Cho, So-Yeon Park, Sayeon Cho, Kwang-Youl Lee, Jae-Hyuk Lee, Kwonseop Kim
δ-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that δ-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind δ-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that δ-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase...
April 30, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29569971/src-family-kinase-inhibitor-bosutinib-enhances-retinoic-acid-induced-differentiation-of-hl-60-leukemia-cells
#7
Robert J MacDonald, Rodica P Bunaciu, Victoria Ip, David Dai, David Tran, Jeffrey D Varner, Andrew Yen
The acute promyelocytic leukemia (APL) has been treated with all-trans retinoic acid (RA) for decades. While RA has largely been ineffective in non-APL AML subtypes, co-treatments combining RA and other agents are currently in clinical trials. Using the RA-responsive non-APL AML cell line HL-60, we tested the efficacy of the Src family kinase (SFK) inhibitor bosutinib on RA-induced differentiation. HL-60 has been recently shown to bear fidelity to a subtype of AML that respond to RA. We found that co-treatment with RA and bosutinib enhanced differentiation evidenced by increased CD11b expression, G1 /G0 cell cycle arrest, and respiratory burst...
March 23, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29558000/hemolytic-uremic-syndrome-with-dual-caution-in-an-infant-cobalamin-c-defect-and-complement-dysregulation-successfully-treated-with-eculizumab
#8
Ulkem Kocoglu Barlas, Hasan Serdar Kıhtır, Nilufer Goknar, Melike Ersoy, Nihal Akcay, Esra Sevketoglu
BACKGROUND: Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS. CASE-DIAGNOSIS/TREATMENT: We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury...
June 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29498809/antibody-based-cell-surface-proteome-profiling-of-metastatic-breast-cancer-primary-explants-and-cell-lines
#9
Vera S Donnenberg, Jayce Jieming Zhang, Erika Moravcikova, Ernest Michael Meyer, Haihui Lu, Christian T Carson, Albert D Donnenberg
Flow cytometric cell surface proteomics provides a new and powerful tool to determine changes accompanying neoplastic transformation and invasion, providing clues to essential interactions with the microenvironment as well as leads for potential therapeutic targets. One of the most important advantages of flow cytometric cell surface proteomics is that it can be performed on living cells that can be sorted for further characterization and functional studies. Here, we document the surface proteome of clonogenic metastatic breast cancer (MBrCa) explants, which was strikingly similar to that of normal mesenchymal stromal cells (P = 0...
April 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29423110/potential-for-subsets-of-wt-npm1-primary-aml-blasts-to-respond-to-retinoic-acid-treatment
#10
Rodica P Bunaciu, Robert J MacDonald, Feng Gao, Lynn M Johnson, Jeffrey D Varner, Xin Wang, Sarah Nataraj, Monica L Guzman, Andrew Yen
Acute myeloid leukemia (AML) has high mortality rates, perhaps reflecting a lack of understanding of the molecular diversity in various subtypes and a lack of known actionable targets. There are currently 12 open clinical trials for AML using combination therapeutic modalities including all- trans retinoic acid (RA). Mutant nucleophosmin-1, proposed as a possible marker for RA response, is the criterion for recruiting patients in three active RA phase 3 clinical trials. We tested the ability of RA alone or in combination with either bosutinib (B) or 6-formylindolo(3,2-b) carbazole (F) to induce conversion of 12 de novo AML samples toward a more differentiated phenotype...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29317233/c-cbl-and-cbl-b-expression-in-skull-base-chordomas-is-associated-with-tumor-progression-and-poor-prognosis
#11
Peng Luo, Xin Wang, Jinpeng Zhou, Long Li, Zhitao Jing
Chordomas are rare, locally aggressive malignancies that are often difficult to eradicate. Surgery and radiotherapy are the first-line treatments, but the probability of local recurrence is high. According to our previous research, c-Cbl and Cbl-b have been linked to tumor progression and poor prognosis of glioma. However, their role in skull base chordomas is unclear. To clarify this issue, in the present study we analyzed the expression of c-Cbl and Cbl-b in relation to the clinicopathological features and clinical outcome of skull base chordomas patients (n=70)...
January 6, 2018: Human Pathology
https://www.readbyqxmd.com/read/29237719/ift20-modulates-ciliary-pdgfr%C3%AE-signaling-by-regulating-the-stability-of-cbl-e3-ubiquitin-ligases
#12
Fabian Marc Schmid, Kenneth Bødtker Schou, Martin Juel Vilhelm, Maria Schrøder Holm, Loretta Breslin, Pietro Farinelli, Lars Allan Larsen, Jens Skorstengaard Andersen, Lotte Bang Pedersen, Søren Tvorup Christensen
Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown...
January 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29196224/phosphorylation-of-mig6-negatively-regulates-the-ubiquitination-and-degradation-of-egfr-mutants-in-lung-adenocarcinoma-cell-lines
#13
Gandhi T K Boopathy, Julia Lim Sze Lynn, Sheena Wee, Jayantha Gunaratne, Wanjin Hong
Activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) leads to the constitutively active kinase, improves the EGFR stability and promotes malignant transformation in lung adenocarcinoma. Despite the clinical significance, the mechanism by which the increased kinase activity stabilizes the receptor is not completely understood. Using SILAC phosphoproteomic approach, we identify that Mig6 is highly phosphorylated at S256 in EGFR mutants (19del and L858R). Loss of Mig6 contributes to the efficient degradation of EGFR wildtype and mutants in lung cancer cells...
March 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29167336/insight-into-the-roles-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-entry-and-trafficking
#14
REVIEW
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cells begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3, and αVβ5), xCT, and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multimolecular complex of receptors, signal molecules (focal adhesion kinase [FAK], Src, phosphatidylinositol 3-kinase [PI3-K], and RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas, and GEF-C3G), actin, and myosin II light chain that lead to virus entry via macropinocytosis...
February 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29114012/cbl-downregulation-increases-rbp4-expression-in-adipocytes-of-female-mice
#15
Gulizar Issa Ameen, Silvia Mora
Obesity leads to adipose tissue dysfunction, insulin resistance and diabetes. Adipose tissue produces adipokines that contribute to regulate insulin sensitivity. In turn, insulin stimulates the production and release of some adipokines. Casitas-b-lymphoma proteins (c-Cbl, Cbl-b and Cbl3) are intracellular adaptor signalling proteins that are rapidly phosphorylated by activation of tyrosine kinase receptors. c-Cbl is rapidly phosphorylated by insulin in adipocytes. Here, we tested the hypothesis that Cbl signalling regulates adipokine expression in adipose tissue...
January 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29079718/correction-for-chakraborty-et-al-c-cbl-mediated-selective-virus-receptor-translocations-into-lipid-rafts-regulate-productive-kaposi-s-sarcoma-associated-herpesvirus-infection-in-endothelial-cells
#16
Sayan Chakraborty, Mohanan ValiyaVeettil, Sathish Sadagopan, Nitika Paudel, Bala Chandran
No abstract text is available yet for this article.
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29067211/pilot-assessment-of-vascular-endothelial-growth-factor-receptors-and-trafficking-pathways-in-recurrent-and-metastatic-canine-subcutaneous-mast-cell-tumours
#17
Lucas Da Silva, Carlos E Fonseca-Alves, Jennifer J Thompson, Robert A Foster, Geoffrey A Wood, Renee L Amorim, Brenda L Coomber
Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF-A, VEGFR2, pVEGFR2, the VEGF co-receptor Neuropilin 1 (NRP-1) and the E3 ubiquitin protein ligase c-Cbl in canine scMCT, and to evaluate their association with disease outcome...
August 2017: Veterinary Medicine and Science
https://www.readbyqxmd.com/read/28986450/stap-2-protein-promotes-prostate-cancer-growth-by-enhancing-epidermal-growth-factor-receptor-stabilization
#18
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 up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown...
November 24, 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
#19
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 TNF-related apoptosis-inducing ligand (TRAIL) sensitivity in cancer cells, 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 this study, DR5, casitas B-lineage lymphoma-b (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...
December 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28846104/berberine-binds-rxr%C3%AE-to-suppress-%C3%AE-catenin-signaling-in-colon-cancer-cells
#20
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
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