keyword
https://read.qxmd.com/read/36470423/free-fatty-acids-stabilize-integrin-%C3%AE-1-via-s-nitrosylation-to-promote-monocyte-endothelial-adhesion
#21
JOURNAL ARTICLE
Qinyu Yao, Qi Cui, Jia Liu, Xinya Xie, Tingting Jiang, Haodong Wang, Ziwei Zhao, Wenfei Zhao, Xiong Du, Baochang Lai, Lei Xiao, Nanping Wang
Hyperlipidemia characterized by high blood levels of free fatty acids (FFA) is important for the progression of inflammatory cardiovascular diseases. Integrin β1 is a transmembrane receptor that drives various cellular functions, including differentiation, migration, and phagocytosis. However, the underlying mechanisms modifying integrin β1 protein and activity in mediating monocyte/macrophage adhesion to endothelium remain poorly understood. In this study, we demonstrated that integrin β1 protein underwent S-nitrosylation in response to nitrosative stress in macrophages...
December 2, 2022: Journal of Biological Chemistry
https://read.qxmd.com/read/36442893/dynamics-and-allosteric-information-pathways-of-unphosphorylated-c-cbl
#22
JOURNAL ARTICLE
Tianyi Yang, Li Han, Shuanghong Huo
Human c-Cbl is a RING-type ligase and plays a central role in the protein degradation cascade. To elucidate its conformational changes related to substrate binding, we performed molecular dynamics simulations of different variants/states of c-Cbl for a cumulative time of 68 μs. Our simulations demonstrate that before the substrate binds, the RING domain samples a broad set of conformational states at a biologically relevant salt concentration, including the closed, partially open, and fully open states, whereas substrate binding leads to a restricted conformational sampling...
November 28, 2022: Journal of Chemical Information and Modeling
https://read.qxmd.com/read/36393850/new-functions-of-c3g-in-platelet-biology-contribution-to-ischemia-induced-angiogenesis-tumor-metastasis-and-tpo-clearance
#23
JOURNAL ARTICLE
Luis Hernández-Cano, Cristina Fernández-Infante, Óscar Herranz, Pablo Berrocal, Francisco S Lozano, Manuel A Sánchez-Martín, Almudena Porras, Carmen Guerrero
C3G is a Rap1 guanine nucleotide exchange factor that controls platelet activation, aggregation, and the release of α-granule content. Transgenic expression of C3G in platelets produces a net proangiogenic secretome through the retention of thrombospondin-1. In a physiological context, C3G also promotes megakaryocyte maturation and proplatelet formation, but without affecting mature platelet production. The aim of this work is to investigate whether C3G is involved in pathological megakaryopoiesis, as well as its specific role in platelet mediated angiogenesis and tumor metastasis...
2022: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/36347273/the-ubiquitination-of-ckip-1-mediated-by-src-aggravates-diabetic-renal-fibrosis-original-article
#24
JOURNAL ARTICLE
Yan Yang, Haiming Xiao, Zeyuan Lin, Rui Chen, Shanshan Li, Chuting Li, Xiaohong Sun, Ziqing Hei, Wenyan Gong, Heqing Huang
Renal chronic inflammation is an important hallmark of diabetic renal fibrosis. Casein kinase 2 interacting protein 1 (CKIP-1) performs a nephroprotective role in the pathogenesis of diabetic nephropathy (DN), which is dramatically decreased in diabetic kidneys. However, whether CKIP-1 regulates inflammation to ameliorate renal fibrosis remains unclear and it is interesting to clarify the degradation mechanism of CKIP-1. Here, we identified CKIP-1 expression was down-regulated in diabetic kidneys and knockout (KO) of CKIP-1 increased c-Jun expression and extra cellular matrix (ECM) in kidneys of normal mice, and knockout (KO) of CKIP-1 further exacerbated renal inflammatory fibrosis in diabetic mice...
November 5, 2022: Biochemical Pharmacology
https://read.qxmd.com/read/36271588/advances-in-the-previous-two-decades-in-our-understanding-of-the-post-translational-modifications-functions-and-drug-perspectives-of-argbp2-and-its-family-members
#25
REVIEW
Siyu Zhang, Yuxin Tong
Arginine kinase-binding protein 2 (ArgBP2) is an adapter protein that belongs to the sorbin homology (SoHo) family. The SoHo family also includes c-Cbl-associated protein (CAP) and vinexin, both of which share structural and functional similarities to ArgBP2. However, the role of SoHo family proteins in cell signaling, drug resistance, metabolism, and diseases, especially cancer, is not fully understood. Herein, we summarize the structure of SoHo family proteins, their post-translational modifications and the comprehensive network of cellular pathways regulated by these proteins, with an emphasis on ArgBP2...
November 2022: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/36086954/targeting-the-ptp1b-bcr-abl1-interaction-for-the-degradation-of-t315i-mutant-bcr-abl1-in-chronic-myeloid-leukemia
#26
JOURNAL ARTICLE
Ahmed Elgehama, Yixuan Wang, Ying Yu, Lin Zhou, Zhixiu Chen, Liwei Wang, Lijun Sun, Jian Gao, Biao Yu, Yan Shen, Qiang Xu
Small molecule induced degradation of mutant Bcr-Abl1 provides a potential approach to overcome Bcr-Abl1 tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML). Our previous study reported that a synthetic steroidal glycoside SBF-1 showed remarkable anti-CML activity by inducing the degradation of native Bcr-Abl1 protein. Here, we observed the comparably growth inhibition for SBF-1 in CML cells harboring T315I mutant Bcr-Abl1 in vitro and in vivo. SBF-1 triggered its degradation through disrupting the interaction between protein-tyrosine phosphatase 1B (PTP1B) and Bcr-Abl1...
September 10, 2022: Cancer Science
https://read.qxmd.com/read/36037968/receptor-kinase-egfr-mapk-adaptor-proteins-mediate-the-epithelial-response-to-candida-albicans-via-the-cytolytic-peptide-toxin-candidalysin
#27
JOURNAL ARTICLE
Nicole O Ponde, Léa Lortal, Antzela Tsavou, Olivia W Hepworth, Don N Wickramasinghe, Jemima Ho, Jonathan P Richardson, David L Moyes, Sarah L Gaffen, Julian R Naglik
Candida albicans (C. albicans) is a dimorphic commensal human fungal pathogen that can cause severe oropharyngeal candidiasis (OPC, oral thrush) in susceptible hosts. During invasive infection, C. albicans hyphae invade oral epithelial cells (OECs) and secrete candidalysin, a pore-forming cytolytic peptide that is required for C. albicans pathogenesis at mucosal surfaces. Candidalysin is produced in the hyphal invasion pocket and triggers cell damage responses in OECs. Candidalysin also activates multiple MAPK-based signaling events that collectively drive the production of downstream inflammatory mediators that coordinate downstream innate and adaptive immune responses...
August 26, 2022: Journal of Biological Chemistry
https://read.qxmd.com/read/35966060/negative-regulation-of-receptor-tyrosine-kinases-by-ubiquitination-key-roles-of-the-cbl-family-of-e3-ubiquitin-ligases
#28
REVIEW
Rong Tang, Wallace Y Langdon, Jian Zhang
Receptor tyrosine kinases (RTKs) serve as transmembrane receptors that participate in a broad spectrum of cellular processes including cellular growth, motility, differentiation, proliferation, and metabolism. Hence, elucidating the regulatory mechanisms of RTKs involved in an assortment of diseases such as cancers attracts increasing interest from researchers. Members of the Cbl family ubiquitin ligases (c-Cbl, Cbl-b and Cbl-c in mammals) have emerged as negative regulators of activated RTKs. Upon activation of RTKs by growth factors, Cbl binds to RTKs via its tyrosine kinase binding (TKB) domain and targets them for ubiquitination, thus facilitating their degradation and negative regulation of RTK signaling...
2022: Frontiers in Endocrinology
https://read.qxmd.com/read/35940046/four-immune-modulating-genes-in-primary-melanoma-that-predict-metastatic-potential
#29
JOURNAL ARTICLE
Jennifer Erdrich, Kristel Lourdault, Alex Judd, David Kaufman, Ke Wei Gong, Melanie Gainsbury, Nan Deng, Wonwoo Shon, Richard Essner
INTRODUCTION: Histologic characteristics cannot adequately predict which patients are at risk of developing metastatic disease after excision of primary cutaneous melanoma. The aim of this study was to identify immunomodulatory genes in primary tumors associated with development of distant metastases. MATERIALS AND METHODS: Thirty-seven patients with primary melanoma underwent surgical excision. RNA was extracted from the primary tumor specimens. cDNA was synthesized and used with Human Gene Expression microarray...
August 5, 2022: Journal of Surgical Research
https://read.qxmd.com/read/35839699/the-abl-abi-signaling-links-wave-regulatory-complex-to-cbl-e3-ubiquitin-ligase-and-is-essential-for-breast-cancer-cell-metastasis
#30
JOURNAL ARTICLE
Peixin Jiang, Suni Tang, Hogan Hudgins, Tate Smalligan, Xue Zhou, Anuja Kamat, Janaki Dharmarpandi, Tarek Naguib, Xinli Liu, Zonghan Dai
The family of Abelson interactor (Abi) proteins is a component of WAVE regulatory complex (WRC) and a downstream target of Abelson (Abl) tyrosine kinase. The fact that Abi proteins also interact with diverse membrane proteins and intracellular signaling molecules places these proteins at a central position in the network that controls cytoskeletal functions and cancer cell metastasis. Here, we identified a motif in Abi proteins that conforms to consensus sequences found in a cohort of receptor and non-receptor tyrosine kinases that bind to Cbl-tyrosine kinase binding domain...
July 12, 2022: Neoplasia: An International Journal for Oncology Research
https://read.qxmd.com/read/35796894/sulfated-glucuronorhamnoxylan-from-capsosiphon-fulvescens-ameliorates-osteoporotic-bone-resorption-via-inhibition-of-osteoclastic-cell-differentiation-and-function-in-vitro-and-in-vivo
#31
JOURNAL ARTICLE
Seong Cheol Kim, Hyeon Jeong Kim, Gi Eun Park, Chang Won Lee, Andriy Synytsya, Peter Capek, Yong Il Park
Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-κB ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model...
August 2022: Marine Biotechnology
https://read.qxmd.com/read/35676290/leukocyte-cell-derived-chemotaxin-2-is-an-antiviral-regulator-acting-through-the-proto-oncogene-met
#32
JOURNAL ARTICLE
Takayoshi Shirasaki, Satoshi Yamagoe, Tetsuro Shimakami, Kazuhisa Murai, Ryu Imamura, Kiyo-Aki Ishii, Hiroaki Takayama, Yukako Matsumoto, Natsumi Tajima-Shirasaki, Naoto Nagata, Ryogo Shimizu, Souma Yamanaka, Atsushi Abe, Hitoshi Omura, Kazunori Kawaguchi, Hikari Okada, Taro Yamashita, Tomoki Yoshikawa, Kazuhiro Takimoto, Motoko Taharaguchi, Shogo Takatsuka, Yoshitsugu Miyazaki, Toshikatsu Tamai, Yamato Tanabe, Makoto Kurachi, Yasuhiko Yamamoto, Shuichi Kaneko, Kunio Matsumoto, Toshinari Takamura, Masao Honda
Retinoic acid-inducible gene (RIG)-I is an essential innate immune sensor that recognises pathogen RNAs and induces interferon (IFN) production. However, little is known about how host proteins regulate RIG-I activation. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine and ligand of the MET receptor tyrosine kinase is an antiviral regulator that promotes the RIG-I-mediated innate immune response. Upon binding to MET, LECT2 induces the recruitment of the phosphatase PTP4A1 to MET and facilitates the dissociation and dephosphorylation of phosphorylated SHP2 from MET, thereby protecting RIG-I from SHP2/c-Cbl-mediated degradation...
June 8, 2022: Nature Communications
https://read.qxmd.com/read/35614042/inhibitory-role-of-proguanil-on-the-growth-of-bladder-cancer-via-enhancing-egfr-degradation-and-inhibiting-its-downstream-signaling-pathway-to-induce-autophagy
#33
JOURNAL ARTICLE
Di Xiao, Xin Hu, Mei Peng, Jun Deng, Sichun Zhou, Simeng Xu, Jingtao Wu, Xiaoping Yang
A major reason for the high mortality of patients with bladder cancer (BC) is that chemotherapy and surgery are only effective for very limited patients. Thus, developing novel treatment options becomes an urgent need for improving clinical outcomes and the quality of life for BC patients. Here, we demonstrated that proguanil significantly inhibited the growth of BC in vitro and in vivo. Importantly, our results indicated that the sensitivity of BC cells to proguanil is positively correlated with the expression of epidermal growth factor receptor (EGFR)...
May 25, 2022: Cell Death & Disease
https://read.qxmd.com/read/35563843/signal-transduction-regulators-in-axonal-regeneration
#34
REVIEW
Barbara Hausott, Rudolf Glueckert, Anneliese Schrott-Fischer, Lars Klimaschewski
Intracellular signal transduction in response to growth factor receptor activation is a fundamental process during the regeneration of the nervous system. In this context, intracellular inhibitors of neuronal growth factor signaling have become of great interest in the recent years. Among them are the prominent signal transduction regulators Sprouty (SPRY) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which interfere with major signaling pathways such as extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3K)/Akt in neurons and glial cells...
May 4, 2022: Cells
https://read.qxmd.com/read/35449154/orp5-promotes-tumor-metastasis-via-stabilizing-c-met-in-renal-cell-carcinoma
#35
JOURNAL ARTICLE
Li Song, Lin Zhang, Yun Zhou, Xiaotong Shao, Yuting Xu, Dongsheng Pei, Qingling Wang
ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo...
April 21, 2022: Cell Death Discovery
https://read.qxmd.com/read/35354799/ablation-of-cbl-b-and-c-cbl-in-dendritic-cells-causes-spontaneous-liver-cirrhosis-via-altering-multiple-properties-of-cd103-cdc1s
#36
JOURNAL ARTICLE
Fei Xu, Chen Liu, Yongli Dong, Wenyan Wu, Jie Xu, Yunqiu Yan, Yu Shao, Chuangli Hao, Yi Yang, Jinping Zhang
The Casitas B-lineage lymphoma (Cbl) family proteins are E3 ubiquitin ligases implicated in the regulation of various immune cells. However, their function in dendritic cells (DCs) remains unclear. To investigate the role of Cbl family members in DCs, we created dendritic cell double-deficient Casitas B lymphoma-b (Cbl-b) and Casitas B lineage lymphoma (c-Cbl) mice by crossing Cbl-b-/- mice with c-Cblflox/flox CD11c-Cre+ mice. We found that specific deletion of Cbl-b and c-Cbl in CD11c+ cells, predominantly in DCs, led to liver fibrosis, cirrhosis, and accumulation of systemic conventional Type I DCs (cDC1s) due to enhanced cell proliferation and decreased cell apoptosis...
March 30, 2022: Cell Death Discovery
https://read.qxmd.com/read/35309168/licochalcone-a-promotes-the-ubiquitination-of-c-met-to-abrogate-gefitinib-resistance
#37
JOURNAL ARTICLE
Shuangze Han, Xiaoying Li, Yu Gan, Wei Li
Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Lico A on c-Met signaling and gefitinib resistance in NSCLC remain unclear. In the present study, Lico A efficiently overcame gefitinib-acquired resistance in NSCLC cells by suppressing c-Met signaling. Lico A decreased cell viability and colony formation dose-dependently and impaired in vivo tumorigenesis of gefitinib-resistant HCC827 and PC-9 cells...
2022: BioMed Research International
https://read.qxmd.com/read/34817293/cten-inhibits-tumor-angiogenesis-and-growth-by-targeting-vegfa-through-down-regulation-of-%C3%AE-catenin-in-breast-cancer
#38
JOURNAL ARTICLE
Xiangdong Lu, Bin Zhou, Minmin Cao, Qin Shao, Yukai Pan, Tao Zhao
C-terminal tensin-like (CTEN) belongs to the tensin gene family, which encodes proteins that localize to focal adhesions and modulate integrin function. Accumulating studies have reported that CTEN expression can be upregulated or downregulated in different types of cancers, suggesting that CTEN has both oncogenic and tumor suppressor functions. In this study, by analyzing the expression level of CTEN in the human breast cancer (BRCA) samples from the clinically annotated genomic database, The Cancer Genome Atlas, we found that CTEN was downregulated in different BRCA subclasses, including luminal, human epidermal growth factor receptor 2 positive and triple-negative BRCA...
2021: Technology in Cancer Research & Treatment
https://read.qxmd.com/read/34729053/downregulation-of-src-family-tyrosine-kinases-by-srcasm-and-c-cbl-a-comparative-analysis
#39
JOURNAL ARTICLE
Vivian Lee, Thomas D Griffin, Yoko Suzuki-Horiuchi, Lily Wushanley, Yerin Kweon, Christine Marshall, Weijie Li, Elias Ayli, Adele Haimovic, Aliya Hines, John T Seykora
AIM: Elevated Src-Family tyrosine kinase (SFK) activity drives carcinogenesis in vivo and elevated SFK activity is found ubiquitously in human cancers. Although human squamous cell carcinomas (SCCs) demonstrate increased SFK activity, in silico analysis of SCCs demonstrates that only 0.4% of lesions contain mutations that could potentially increase SFK activity; similarly, a low frequency of activating SFK mutations is found in other major cancers. These findings indicate that SFK activation in cancers likely is not due to activating mutations but alternative mechanisms...
2021: Journal of Carcinogenesis
https://read.qxmd.com/read/34725941/modulation-of-intrinsic-inhibitory-checkpoints-using-nano-carriers-to-unleash-nk-cell-activity
#40
JOURNAL ARTICLE
Guy Biber, Batel Sabag, Anat Raiff, Aviad Ben-Shmuel, Abhishek Puthenveetil, Jennifer I C Benichou, Tammir Jubany, Moria Levy, Shiran Killner, Mira Barda-Saad
Natural killer (NK) cells provide a powerful weapon mediating immune defense against viral infections, tumor growth, and metastatic spread. NK cells demonstrate great potential for cancer immunotherapy; they can rapidly and directly kill cancer cells in the absence of MHC-dependent antigen presentation and can initiate a robust immune response in the tumor microenvironment (TME). Nevertheless, current NK cell-based immunotherapies have several drawbacks, such as the requirement for ex vivo expansion of modified NK cells, and low transduction efficiency...
January 11, 2022: EMBO Molecular Medicine
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