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Wang Z.,University of California at Davis | Wang Z.,CAS Institute of Biophysics | Fan M.,University of California at Davis | Candas D.,University of California at Davis | And 13 more authors.
Developmental Cell

A substantial amount of mitochondrial energy is required for cell-cycle progression. The mechanisms underlying the coordination of the mitochondrial respiration with cell-cycle progression, especially the G2/M transition, remain to be elucidated. Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. Mitochondria-targeted cyclin B1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cell-cycle time. Thus, cyclin B1/Cdk1-mediated phosphorylation of mitochondrial substrates allows cells to sense and respond to increased energy demand for G2/M transition and, subsequently, to upregulate mitochondrial respiration for successful cell-cycle progression. © 2014 Elsevier Inc. Source

Hu Z.,CAS National Center for Nanoscience and Technology | Hu Z.,Institute for Systems Biology | Hu Z.,Beijing Proteomics Research Center | Lausted C.,Institute for Systems Biology | And 7 more authors.

We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane- bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks. © Ivyspring International Publisher. Source

Fu H.-Y.,301 Militry Hospital of China | Fu H.-Y.,Beijing Institute of Radiation Medicine | Yuan J.,Beijing Institute of Radiation Medicine | Yuan J.,Beijing Proteomics Research Center | And 20 more authors.
Fenxi Huaxue/ Chinese Journal of Analytical Chemistry

Polypeptide antibody pre-concentration method coupled with mass spectrometry have been established for determination of serum polypeptide. Polypeptide was captured by agarose beads followed by binding of specific polyclonal antibodies from serum. After timed washing steps, the remaining bound polypeptides were eluted from the beads and detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The ion signals of protein A agarose bead-based platform amenable to high throughput peptide capture followed by mass spectrometry were achieved with enough precision (RSD < 12%) and accuracy (about 10% relative error) for quantifying biomarkers in the physiologically relevant nM range. The method to detect pep5 in the clinical hepatocellular carcinoma serum had the sensitivity of 78.0% and specificity of 90%. The method is appropriate for the detection of low concentration biomarkers in clinical samples, and it will be significant for earlier diagnosis of cancers. Copyright © 2012, Changchun Institute of Applied Chemistry. Source

Huang R.,Beijing Institute of Radiation Medicine | Huang R.,Beijing Proteomics Research Center | Huang R.,State Key Laboratory of Proteomics | Yu M.,Beijing Institute of Radiation Medicine | And 23 more authors.
Proteomics - Clinical Applications

Purpose: The eukaryotic cytosolic chaperonin containing TCP-1 (CCT) plays an important role in maintaining cellular homeostasis by assisting the folding of many proteins and is also well known for the critical roles in disease. However, the functions of CCT complex have not been established globally, especially when translocating into nuclear. The purpose of this study is to explore the function of CCT in nuclear and present a strategy in clinical proteomics studies. Experimental design: Blue native polyacrylamide gel electrophoresis (BN-PAGE) combined with mass spectrometry was applied to separate and identify CCT protein complexes. Results: We isolated the CCT complex in K562 nucleus and identified a novel CCT complex containing 40 protein components involved in protein folding, RNA processing, apoptosis, and cell metabolism. The interactions between four candidate proteins and CCT were confirmed by immunoblotting. Computational biological analyses and independent biochemical assays validated the overall quality of interactions. Conclusions and clinical relevance: Our results support clues that CCT might play an unexpected role in various biological processes including RNA processing. And we envision future applications for this system searching for new clues of CCT in disease and readily be applied to the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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