Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Mepe/Of45 Protects Cells From Dna Damage Induced Killing Via Stabilizing Chk1., Shuang Liu, Hongyan Wang, Xiang Wang, Lin Lu, Ning Gao, Peter S N Rowe, Baocheng Hu, Ya Wang
Mepe/Of45 Protects Cells From Dna Damage Induced Killing Via Stabilizing Chk1., Shuang Liu, Hongyan Wang, Xiang Wang, Lin Lu, Ning Gao, Peter S N Rowe, Baocheng Hu, Ya Wang
Department of Radiation Oncology Faculty Papers
Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the …
Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti
Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti
Farber Institute for Neuroscience Faculty Papers
Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
Department of Dermatology and Cutaneous Biology Faculty Papers
We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …
Systems-Level Interactions Between Insulin-Egf Networks Amplify Mitogenic Signaling., Nikolay Borisov, Edita Aksamitiene, Anatoly Kiyatkin, Stefan Legewie, Jan Berkhout, Thomas Maiwald, Nikolai P Kaimachnikov, Jens Timmer, Jan B Hoek, Boris N Kholodenko
Systems-Level Interactions Between Insulin-Egf Networks Amplify Mitogenic Signaling., Nikolay Borisov, Edita Aksamitiene, Anatoly Kiyatkin, Stefan Legewie, Jan Berkhout, Thomas Maiwald, Nikolai P Kaimachnikov, Jens Timmer, Jan B Hoek, Boris N Kholodenko
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Crosstalk mechanisms have not been studied as thoroughly as individual signaling pathways. We exploit experimental and computational approaches to reveal how a concordant interplay between the insulin and epidermal growth factor (EGF) signaling networks can potentiate mitogenic signaling. In HEK293 cells, insulin is a poor activator of the Ras/ERK (extracellular signal-regulated kinase) cascade, yet it enhances ERK activation by low EGF doses. We find that major crosstalk mechanisms that amplify ERK signaling are localized upstream of Ras and at the Ras/Raf level. Computational modeling unveils how critical network nodes, the adaptor proteins GAB1 and insulin receptor substrate (IRS), Src kinase, …
Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa
Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa
Department of Urology Faculty Papers
Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …
Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta
Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta
Kimmel Cancer Center Faculty Papers
BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is …