7 results on '"Yuanyu Hu"'
Search Results
2. PKCδ mediates Nrf2-dependent protection of neuronal cells from NO-induced apoptosis
- Author
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Yuanyu Hu, Poh Yong Ng, Jindan Zhang, Keiichi I. Nakayama, Saravanakumar Dhakshinamoorthy, Alan G. Porter, Baojie Li, and Amos C. Hung
- Subjects
NF-E2-Related Factor 2 ,Biophysics ,Apoptosis ,Biology ,Nitric Oxide ,Biochemistry ,Nitric oxide ,Mice ,chemistry.chemical_compound ,Genes, Reporter ,Gene expression ,NAD(P)H Dehydrogenase (Quinone) ,medicine ,Animals ,Combinatorial Chemistry Techniques ,Luciferases ,Protein Kinase Inhibitors ,Molecular Biology ,Cells, Cultured ,Neurons ,NADPH Dehydrogenase ,Wild type ,Cell Biology ,Molecular biology ,Cell biology ,Protein Kinase C-delta ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Gene Knockdown Techniques ,NAD+ kinase ,Neuron ,Signal transduction ,Rottlerin ,Heme Oxygenase-1 - Abstract
A chemical inhibitor library of 84 compounds was screened to investigate the signaling pathway(s) leading to activation of Nrf2 in response to nitric oxide (NO). We identified the protein kinase C delta (PKCdelta) inhibitor rottlerin as the only compound that reduced NO-induced ARE-luciferase reporter activity and diminished NO-induced up-regulation of two Nrf2/ARE-regulated proteins - NAD(P)H:quinone oxidoreductase-1 (NQO1) and hemeoxygenase-1 (HO-1) in SH-Sy5y cells. Rottlerin also sensitized neuroblastoma cells and mouse primary cortical neurons to NO-induced apoptosis. Stable over-expression of PKCdelta augmented NO-induced, ARE-dependent gene expression of HO-1 in SH-Sy5y cells, which were more protected from NO killing. Conversely, NO-induced ARE-dependent gene expression was reduced in PKCdelta-knockdown SH-EP cells, which displayed greater sensitivity to apoptosis. PKCdelta(-/-) cortical neurons exhibited increased NO-induced apoptosis and less HO-1 mRNA and protein induction compared with wild type neurons. Hence, PKCdelta is an important positive modulator of NO-induced Nrf2/ARE-dependent signaling that counteracts NO-mediated apoptosis in neuronal cells.
- Published
- 2009
3. Atypical Atm-p53 genetic interaction in osteogenesis is mediated by Smad1 signaling
- Author
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Aijun Hao, Bi Jin Au, Yuanyu Hu, Lili Li, Lin He, Deyong Jia, Baojie Li, Gang Ma, James Yeh, Huijuan Liu, and Jenny Fung Ling Chau
- Subjects
Cell Cycle Proteins ,Plasma protein binding ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,DNA-binding protein ,Smad1 Protein ,Mice ,Osteogenesis ,Genetics ,Animals ,Humans ,Cell Cycle Protein ,Molecular Biology ,Mice, Knockout ,Genetic interaction ,Protein-Serine-Threonine Kinases ,Osteoblasts ,Chemistry ,Tumor Suppressor Proteins ,Cell Cycle ,Cell Biology ,General Medicine ,Cell cycle ,Cell biology ,DNA-Binding Proteins ,Signal transduction ,Tumor Suppressor Protein p53 ,Protein Binding ,Signal Transduction - Published
- 2012
4. c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16INK4a expression
- Author
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Baojie Li, Deyong Jia, Guo Qiang Chen, Xueying Wang, Lin He, Stephen P. Goff, Gang Ma, Li Xia, Wai Fook Leong, Yuanyu Hu, Ye-Guang Chen, Lili Li, Jenny Fung Ling Chau, Hui Yi Kua, James Yeh, Yuji Mishina, Sharon Boast, and Huijuan Liu
- Subjects
MAPK/ERK pathway ,Senescence ,Inhibitor of Differentiation Protein 1 ,Smad5 Protein ,Time Factors ,Genotype ,Molecular Sequence Data ,Bone morphogenetic protein ,Bone Morphogenetic Protein Receptors, Type II ,Transfection ,Article ,Smad1 Protein ,Mice ,hemic and lymphatic diseases ,medicine ,Animals ,Amino Acid Sequence ,Phosphorylation ,Proto-Oncogene Proteins c-abl ,neoplasms ,Bone Morphogenetic Protein Receptors, Type I ,Cells, Cultured ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Mice, Knockout ,Mitogen-Activated Protein Kinase 1 ,ABL ,Mitogen-Activated Protein Kinase 3 ,Osteoblasts ,Chemistry ,Osteoblast ,Mesenchymal Stem Cells ,Cell Biology ,MAP Kinase Kinase Kinases ,BMPR1A ,BMPR2 ,Cell biology ,Enzyme Activation ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Phenotype ,Smad8 Protein ,embryonic structures ,Bone Morphogenetic Proteins ,Tumor Suppressor Protein p53 ,Signal Transduction - Abstract
Defects in stem cell renewal or progenitor cell expansion underlie ageing-related diseases such as osteoporosis. Yet much remains unclear about the mechanisms regulating progenitor expansion. Here we show that the tyrosine kinase c-Abl plays an important role in osteoprogenitor expansion. c-Abl interacts with and phosphorylates BMPRIA and the phosphorylation differentially influences the interaction of BMPRIA with BMPRII and the Tab1-Tak1 complex, leading to uneven activation of Smad1/5/8 and Erk1/2, the canonical and non-canonical BMP pathways that direct the expression of p16(INK4a). c-Abl deficiency shunts BMP signalling from Smad1/5/8 to Erk1/2, leading to p16(INK4a) upregulation and osteoblast senescence. Mouse genetic studies revealed that p16(INK4a) controls mesenchymal stem cell maintenance and osteoblast expansion and mediates the effects of c-Abl deficiency on osteoblast expansion and bone formation. These findings identify c-Abl as a regulator of BMP signalling pathways and uncover a role for c-Abl in p16(INK4a) expression and osteoprogenitor expansion.
- Published
- 2011
5. PKC delta phosphorylates p52ShcA at Ser29 to regulate ERK activation in response to H2O2
- Author
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Charlene Kang, Baojie Li, Yuanyu Hu, and Robin J. Philp
- Subjects
MAPK/ERK pathway ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,Gene Expression Regulation, Enzymologic ,Cell Line ,Enzyme activator ,Mice ,Transduction, Genetic ,Serine ,Animals ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Protein Kinase C ,Adaptor Proteins, Signal Transducing ,Regulation of gene expression ,Chemistry ,Signal transducing adaptor protein ,Cell Biology ,Hydrogen Peroxide ,Cell biology ,Enzyme Activation ,Oxidative Stress ,Shc Signaling Adaptor Proteins ,Cell culture ,Cytoplasm ,NIH 3T3 Cells ,Signal transduction ,Signal Transduction - Abstract
Both PKC delta and ShcA have been implicated in cell response to oxidative stress [Y. Hu, X. Wang, L. Zeng, D.Y. Cai, K. Sabapathy, S.P. Goff, E.J. Firpo, B. Li, Mol Biol Cell., 16 (2005) 3705-3718, B. Li, X. Wang, N. Rasheed, Y. Hu, S. Boast, T. Ishii, K. Nakayama, K.I. Nakayama, S.P., Goff, Genes Dev, 18 (2004) 1824-1837, E. Migliaccio, M. Giorgio, S. Mele, G. Pelicci, P. Reboldi, P.P. Pandolfi, L. Lanfrancone, P.G. Pelicci, Nature, 402 (1999) 309-313], yet their relationship in the response has not been studied. Here we report that PKC delta interacts with ShcA and this interaction is promoted by H(2)O(2). PKC delta and ShcA are also colocalized in the cytoplasm and displayed co-translocation in response to H(2)O(2). Activated PKC delta was able to phosphorylate ShcA at Ser29, as determined by mass spectrometry. These results suggest that ShcA, p66 and p52, are substrates that interact with PKC delta. This phosphorylation is critical in H(2)O(2) induced ERK activation as reconstitution with ShcA Ser29A failed to rescue ERK activation of ShcA-/- MEFs, while ShcA could. In line with this conclusion, inhibition of PKC delta with inhibitors is able to diminish H(2)O(2) induced ERK activation in MEFs. These results suggest that the interaction between PKC delta and ShcA and the phosphorylation of ShcA at Ser29 play important roles in ERK activation in cell response to H(2)O(2).
- Published
- 2006
6. ERK phosphorylates p66shcA on Ser36 and subsequently regulates p27kip1 expression via the Akt-FOXO3a pathway: implication of p27kip1 in cell response to oxidative stress
- Author
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Li Zeng, Stephen P. Goff, Eduardo Firpo, De-Yu Cai, Kanaga Sabapathy, Yuanyu Hu, Xueying Wang, and Baojie Li
- Subjects
MAPK/ERK pathway ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,Biology ,medicine.disease_cause ,chemistry.chemical_compound ,Mice ,medicine ,Serine ,Animals ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Protein kinase B ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Regulation of gene expression ,Mice, Knockout ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,Kinase ,Forkhead Box Protein O3 ,Tyrosine phosphorylation ,Forkhead Transcription Factors ,Cell Biology ,Hydrogen Peroxide ,Articles ,Cell biology ,Enzyme Activation ,Oxidative Stress ,chemistry ,Gene Expression Regulation ,Shc Signaling Adaptor Proteins ,Signal transduction ,Oxidative stress ,Protein Binding ,Signal Transduction - Abstract
Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.
- Published
- 2005
7. Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C δ
- Author
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Sharon Boast, Yuanyu Hu, Xueying Wang, Tetsuro Ishii, Naslin Rasheed, Baojie Li, Stephen P. Goff, Keiichi I. Nakayama, and Keiko Nakayama
- Subjects
Molecular biology ,Apoptosis ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,medicine.disease_cause ,Antioxidants ,Mice ,hemic and lymphatic diseases ,Proto-Oncogene Proteins c-abl ,Protein Kinase C ,chemistry.chemical_classification ,Mice, Knockout ,Reverse Transcriptase Polymerase Chain Reaction ,Homozygote ,Research Papers ,Up-Regulation ,DNA-Binding Proteins ,Protein Kinase C-delta ,Phenotype ,Peroxidases ,Arsenates ,Subcellular Fractions ,Programmed cell death ,DNA damage ,NF-E2-Related Factor 2 ,Biology ,Protein Serine-Threonine Kinases ,Phospholipases A ,Enzyme activator ,Downregulation and upregulation ,Developmental biology ,medicine ,Genetics ,Animals ,Protein kinase C ,Reactive oxygen species ,Leucine Zippers ,Osteoblasts ,Herbicides ,Tumor Suppressor Proteins ,Peroxiredoxins ,Enzyme Activation ,Oxidative Stress ,Retroviridae ,chemistry ,FOS: Biological sciences ,Trans-Activators ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species ,Oxidative stress - Abstract
c-Abl and Atm have been implicated in cell responses to DNA damage and oxidative stress. However, the molecular mechanisms by which they regulate oxidative stress response remain unclear. In this report, we show that deficiency of c-Abl and deficiency of ATM differentially altered cell responses to oxidative stress by induction of antioxidant protein peroxiredoxin I (Prx I) via Nrf2 and cell death, both of which required protein kinase C (PKC) δ activation and were mediated by reactive oxygen species. c-abl-/- osteoblasts displayed enhanced Prx I induction, elevated Nrf2 levels, and hypersusceptibility to arsenate, which were reinstated by reconstitution of c-Abl; Atm-/- osteoblasts showed the opposite. These phenotypes correlated with increased PKC δ expression in c-abl-/- osteoblasts and decreased PKC δ expression in Atm-/- cells, respectively. The enhanced responses of c-abl-/- osteoblasts could be mimicked by overexpression of PKC δ in normal cells and impeded by inhibition of PKC δ, and diminished responses of Atm-/- cells could be rescued by PKC δ overexpression, indicating that PKC δ mediated the effects of c-Abl and ATM in oxidative stress response. Hence, our results unveiled a previously unrecognized mechanism by which c-Abl and Atm participate in oxidative stress response.
- Published
- 2004
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