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https://www.readbyqxmd.com/read/29655550/proteomic-investigating-the-cooperative-lethal-effect-of-egfr-and-mdm2-inhibitors-on-ovarian-carcinoma
#1
Shing-Jyh Chang, En-Chi Liao, Hsin-Yueh Yeo, Wen-Hong Kuo, Hsin-Yi Chen, Yi-Ting Tsai, Yu-Shan Wei, Ying-Jen Chen, Yi-Shiuan Wang, Ji-Min Li, Chuan-Chi Shih, Chia-Hao Chan, Hsiu-Chuan Chou, Yung-Jen Chuang, Hong-Lin Chan
With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate...
April 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29628507/%C3%AE-np73-enhances-hif-1%C3%AE-protein-stability-through-repression-of-the-ecv-complex
#2
Marina Stantic, Johanna Wolfsberger, Habib A M Sakil, Margareta T Wilhelm
Cellular responses to low oxygen conditions are mainly regulated by the Hypoxia-inducible factors (HIFs). Induction of HIF-1α in tumor cells activates the angiogenic switch and allows for metabolic adaptations. HIF-1α protein levels are tightly regulated through ubiquitin-mediated proteosomal degradation; however, high levels of HIF-1α is a common feature in many solid tumors and is thought to enhance cancer cell proliferation, migration, and survival. Here, we report that the oncogenic p73 isoform, ∆Np73, increases HIF-1α protein stability...
April 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29628506/zinc-finger-protein-746-promotes-colorectal-cancer-progression-via-c-myc-stability-mediated-by-glycogen-synthase-kinase-3%C3%AE-and-f-box-and-wd-repeat-domain-containing-7
#3
Ji Hoon Jung, Deok-Beom Jung, Hyunseok Kim, Hyemin Lee, Shi-Eun Kang, Sanjay K Srivastava, Miyong Yun, Sung-Hoon Kim
To elucidate the underlying oncogenic mechanism of zinc finger protein 746 (ZNF746), current study was conducted in colorectal cancers (CRCs). Herein, ZNF746 was overexpressed in HCT116, SW620, and SW480 cells, which was supported by CRC tissue microarray and TCGA analysis. Also, DNA microarray revealed the differentially expressed gene profile particularly related to cell cycle genes and c-Myc in ZNF746 depleted HCT116 cells. Furthermore, ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization by immunoprecipitation and immunofluorescence, while ZNF746 and c-Myc exist mainly in nucleoplasm...
April 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29588478/ikaros-family-zinc-finger-1-regulates-dendritic-cell-development-and-function-in-humans
#4
Urszula Cytlak, Anastasia Resteu, Delfien Bogaert, Hye Sun Kuehn, Thomas Altmann, Andrew Gennery, Graham Jackson, Attila Kumanovics, Karl V Voelkerding, Seraina Prader, Melissa Dullaers, Janine Reichenbach, Harry Hill, Filomeen Haerynck, Sergio D Rosenzweig, Matthew Collin, Venetia Bigley
Ikaros family zinc finger 1 (IKZF1) is a haematopoietic transcription factor required for mammalian B-cell development. IKZF1 deficiency also reduces plasmacytoid dendritic cell (pDC) numbers in mice, but its effects on human DC development are unknown. Here we show that heterozygous mutation of IKZF1 in human decreases pDC numbers and expands conventional DC1 (cDC1). Lenalidomide, a drug that induces proteosomal degradation of IKZF1, also decreases pDC numbers in vivo, and reduces the ratio of pDC/cDC1 differentiated from progenitor cells in vitro in a dose-dependent manner...
March 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29580840/hiv-1-promotes-the-degradation-of-components-of-the-type-1-ifn-jak-stat-pathway-and-blocks-anti-viral-isg-induction
#5
Siobhan Gargan, Suaad Ahmed, Rebecca Mahony, Ciaran Bannan, Silvia Napoletano, Cliona O'Farrelly, Persephone Borrow, Colm Bergin, Nigel J Stevenson
Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner...
March 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29553845/nano-gold-displayed-anti-inflammatory-property-via-nf-kb-pathways-by-suppressing-cox-2-activity
#6
Mahmood Ahmad Khan, Mohd Jahir Khan
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, affecting almost 1% of world population. Although the exact cause of RA is not known but the complex interaction between inflammatory mediators like tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) is accountable for cartilage destruction in joints. Gold is used for arthritis treatment since long without knowing its mechanism of action. Hence, the present study was designed to assess antiarthritic activity of nanogold (AuNGs) in collagen-induced arthritic (CIA) rat model by virtue of decreasing inflammatory mediators and oxidative stress...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29523886/bortezomib-is-safe-in-and-stabilizes-pulmonary-function-in-patients-with-allo-hsct-associated-pulmonary-cgvhd
#7
Manu Jain, Grs Budinger, Borko Jovanovic, Jane Dematte, Sara Duffey, Jayesh Mehta
Pulmonary chronic graft-versus-host disease (p-CGVHD) following allogeneic HSCT is devastating with limited proven treatments. Although sporadically associated with pulmonary toxicity, the proteasome inhibitor bortezomib may be efficacious in p-CGVHD. We sought to establish safety and tolerability of bortezomib in pilot, open-label trial of patients with p-CGVHD. The primary endpoint was adverse events. Efficacy was assessed by comparing FEV1 decline prior to p-CGVHD diagnosis to during the bortezomib treatment period...
March 9, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29507502/progressive-multifocal-leukoencephalopathy-during-ixazomib-based-chemotherapy
#8
C P Sawicki, S A Climans, C C Hsia, J A Fraser
Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid...
February 2018: Current Oncology
https://www.readbyqxmd.com/read/29496961/mapk-signaling-couples-scf-mediated-degradation-of-translational-regulators-to-oocyte-meiotic-progression
#9
Edyta Kisielnicka, Ryuji Minasaki, Christian R Eckmann
RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evolutionarily conserved translational regulators (CPB-3/CPEB and GLD-1/STAR) to proteosomal degradation in Caenorhabditis elegans germ cells at the transition from pachytene to diplotene of meiotic prophase. Both RBPs are recognized by the same ubiquitin ligase complex, containing the molecular scaffold Cullin-1 and the tumor suppressor SEL-10/FBXW7 as its substrate recognition subunit...
March 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29481571/17-aag-inhibits-vemurafenib-associated-map-kinase-activation-and-is-synergistic-with-cellular-immunotherapy-in-a-murine-melanoma-model
#10
Sandeep S Joshi, Shunlin Jiang, Emmanual Unni, Stephen R Goding, Tao Fan, Paul A Antony, Thomas J Hornyak
Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF...
2018: PloS One
https://www.readbyqxmd.com/read/29465084/protein-kinase-d1-regulates-subcellular-localisation-and-metastatic-function-of-metastasis-associated-protein-1
#11
Aditya Ganju, Subhash C Chauhan, Bilal Bin Hafeez, Kyle Doxtater, Manish K Tripathi, Nadeem Zafar, Murali M Yallapu, Rakesh Kumar, Meena Jaggi
BACKGROUND: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1. METHODS: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were determined using western blotting and reverse-transcription quantitative real-time PCR...
February 20, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29423113/cks1-expression-in-melanocytic-nevi-and-melanoma
#12
Anna A Brożyna, Andrew Aplin, Cynthia Cohen, Grant Carlson, Andrew Joseph Page, Michael Murphy, Andrzej T Slominski, J Andrew Carlson
Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29367551/the-potential-of-a-novel-class-of-epac-selective-agonists-to-combat-cardiovascular-inflammation
#13
REVIEW
Graeme Barker, Euan Parnell, Boy van Basten, Hanna Buist, David R Adams, Stephen J Yarwood
The cyclic 3',5'-adenosine monophosphate (cAMP) sensor enzyme, EPAC1, is a candidate drug target in vascular endothelial cells (VECs) due to its ability to attenuate proinflammatory cytokine signalling normally associated with cardiovascular diseases (CVDs), including atherosclerosis. This is through the EPAC1-dependent induction of the suppressor of cytokine signalling gene, SOCS3, which targets inflammatory signalling proteins for ubiquitinylation and destruction by the proteosome. Given this important role for the EPAC1/SOCS3 signalling axis, we have used high throughput screening (HTS) to identify small molecule EPAC1 regulators and have recently isolated the first known non-cyclic nucleotide (NCN) EPAC1 agonist, I942...
December 5, 2017: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29363325/short-term-high-glucose-treatment-decreased-abundance-of-orai1-protein-through-posttranslational-mechanisms-in-rat-mesangial-cells
#14
Hui Jiang, Shubiao Zou, Sarika Chaudhari, Rong Ma
The short-term effect of high glucose (HG) treatment on store-operated Ca2+ entry in mesangial cells (MCs) is not well known. The aim of the present study was to determine whether and how HG treatment for a short period altered protein abundance of Orai1, the channel mediating store-operated Ca2+ entry in MCs. Rat and human MCs were exposed to HG (25 mM) for 2, 4, 8, and 24 hours and the abundance of Orai1 protein was significantly decreased at the time point of 8 and 16 hours. Consistently, HG treatment for 8 hours significantly reduced store-operated Ca2+ entry in rat MCs...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29355525/negative-regulation-of-brca1-by-transforming-acidic-coiled-coil-protein-3-tacc3
#15
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Eun-Kyoung Breuer
In spite of the push to identify modifiers of BRCAness, it still remains unclear how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or epigenetic aberrations. Mounting evidence indicates that the transforming acidic coiled-coil 3 (TACC3) plays an important role in the centrosome-microtubule network during mitosis and gene expression, and that deregulation of TACC3 is associated with breast cancer. However, the molecular mechanisms by which TACC3 contributes to breast cancer development have yet to be elucidated...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#16
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancer-a
#17
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 24, 2018: Small GTPases
https://www.readbyqxmd.com/read/29282318/src1-promotes-th17-differentiation-by-overriding-foxp3-suppression-to-stimulate-ror%C3%AE-t-activity-in-a-pkc-%C3%AE-dependent-manner
#18
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29260173/fucoidan-inhibits-amyloid-%C3%AE-induced-toxicity-in-transgenic-caenorhabditis-elegans-by-reducing-the-accumulation-of-amyloid-%C3%AE-and-decreasing-the-production-of-reactive-oxygen-species
#19
Xuelian Wang, Kaixuan Yi, Yan Zhao
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. As the aging population is increasing, AD is becoming one of the leading causes of disability and death among the elderly. However, currently there is no cure for this disease. Fucoidan is a complex sulfated polysaccharide mainly found in brown seaweed. Recent studies have shown that fucoidan is neuroprotective and may have potential to be used for treating and/or preventing neurodegenerative diseases such as AD. In this study, we investigated the effects and possible mechanisms of fucoidan on Abeta induced toxicity in a transgenic Caenorhabditis elegans (C...
January 24, 2018: Food & Function
https://www.readbyqxmd.com/read/29258576/tsetse-fly-glossina-pallidipes-midgut-responses-to-trypanosoma-brucei-challenge
#20
Rosemary Bateta, Jingwen Wang, Yineng Wu, Brian L Weiss, Wesley C Warren, Grace A Murilla, Serap Aksoy, Paul O Mireji
BACKGROUND: Tsetse flies (Glossina spp.) are the prominent vector of African trypanosome parasites (Trypanosoma spp.) in sub-Saharan Africa, and Glossina pallidipes is the most widely distributed species in Kenya. This species displays strong resistance to infection by parasites, which are typically eliminated in the midgut shortly after acquisition from the mammalian host. Although extensive molecular information on immunity for the related species Glossina morsitans morsitans exists, similar information is scarce for G...
December 19, 2017: Parasites & Vectors
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