Time filter

Source Type

Laboratory of, China

Zhang R.-R.,Chinese Academy of Sciences | Cui Q.-Y.,Chinese Academy of Sciences | Murai K.,Beckman Research Institute | Lim Y.C.,Agency for Science, Technology and Research Singapore | And 18 more authors.
Cell Stem Cell | Year: 2013

DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in embryonic stem cells and neurons in mammals. However, its biological function in vivo is largely unknown. Here, we demonstrate that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain. Mice lacking Tet1 exhibit impaired hippocampal neurogenesis accompanied by poor learning and memory. In adult neural progenitor cells deficient in Tet1, a cohort of genes involved in progenitor proliferation were hypermethylated and downregulated. Our results indicate that Tet1 is positively involved in the epigenetic regulation of neural progenitor cell proliferation in the adult brain. © 2013 Elsevier Inc. Source

Yan B.,Tongji University | Yan B.,Harvard University | Kong M.,Harvard University | Chen S.,Harvard University | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2010

Livin is a member of inhibitors of apoptosis proteins (IAPs) and overexpressed in transformed cells and several cancers. Although strategies to decrease Livin levels have been conducted for rational cancer therapy, the molecular mechanism controlling Livin expression in tumors has not been completely elucidated. Here, we show that vascular endothelial growth factor (VEGF) stimulation can increase Livin expression in HeLa cells or SK-MEL-28 cells. This response is independent of de novo gene transcription or changes in mRNA expression but occurs at protein expression levels. VEGF stimulation results in mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein. Livin silencing, Rapamycin alone or in combination with cytotoxic agent can reduce Livin protein levels, and decrease cells viability. Thus, ablation of Livin translation contributes to remove an anti-apoptotic mechanism potentially contributing to aggressive tumor behavior. Pharmacologic inhibition of VEGF/mTOR/Livin signaling may provide a novel strategy for cancer treatment. © 2010 Wiley-Liss, Inc. Source

Yang Y.,Key Laboratory of Arrhythmias | Yang Y.,Dalian Medical University | Yang Y.,Tongji University | Liang B.,Danish National Research Foundation Center for Cardiac Arrhythmia | And 32 more authors.
American Journal of Human Genetics | Year: 2010

Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS. © 2010 The American Society of Human Genetics. Source

Qin Z.,Medical University of South Carolina | Qin Z.,Key Laboratory of Arrhythmias | Qin Z.,Tongji University | Dai L.,Medical University of South Carolina | And 6 more authors.
Leukemia | Year: 2011

The Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), for which cytotoxic chemotherapy represents the standard of care. The high mortality associated with PEL may be explained in part by resistance of these tumors to chemotherapy. The membrane-bound glycoprotein emmprin (CD147) enhances chemoresistance in tumors through effects on transporter expression, trafficking and interactions. Interactions between hyaluronan and hyaluronan receptors on the cell surface also facilitate emmprin-mediated chemoresistance. Whether emmprin or hyaluronan-receptor interactions regulate chemotherapeutic resistance for virus-associated malignancies is unknown. Using human PEL tumor cells, we found that PEL sensitivity to chemotherapy is directly proportional to expression of emmprin, the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and a drug transporter known as the breast cancer resistance protein/ABCG2 (BCRP), and that emmprin, LYVE-1 and BCRP interact with each other and colocalize on the PEL cell surface. In addition, we found that emmprin induces chemoresistance in PEL cells through upregulation of BCRP expression, and RNA interference targeting of emmprin, LYVE-1 or BCRP enhances PEL cell apoptosis induced by chemotherapy. Finally, disruption of hyaluronan-receptor interactions using small hyaluronan oligosaccharides reduces expression of emmprin and BCRP while sensitizing PEL cells to chemotherapy. Collectively, these data support interdependent roles for emmprin, LYVE-1 and BCRP in chemotherapeutic resistance for PEL. © 2011 Macmillan Publishers Limited All rights reserved. Source

Yan B.,Tongji University | Yan B.,Harvard University | Yan B.,Key Laboratory of Arrhythmias | Kong M.,Harvard University | And 2 more authors.
Molecular and Cellular Biochemistry | Year: 2011

Bax induces mitochondrial-dependent cell apoptosis signals in mammalian cells. However, the mechanism of how Bax is kept inactive is not fully elucidated. Here, we identify FIH1 as a potential interactor of Bax through mass spectrometry analysis. Coimmunoprecipitation and GST pull-down experiments show that FIH1 can directly interact with Bax. Bax-mediated apoptosis is suppressed by FIH1 overexpression, but accelerated by FIH1 deficiency. FIH1 functions as a cytosol retention factor of Bax, blocking Bax translocation from cytosol to mitochondria in response to apoptotic stimuli. Overall, there results unveil a novel role of FIH1 in the regulation of Bax-mediated apoptosis. © 2010 Springer Science+Business Media, LLC. Source

Discover hidden collaborations