Accounting for Protein Subcellular Localization: A Compartmental Map of the Rat Liver Proteome

Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle whereas a significant fraction may reside elsewhere. As a step toward a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this data set, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at 6 months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.     

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

Background & Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.

Design

Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.

Results

We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r² = 0.64, p<0.05), fibrosis (r² = 0.66, p<0.05) and pathological angiogenesis (r² = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.

Conclusions

These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.     

血浆蛋白质组——人类蛋白质组计划的“探路者”

概述了血浆蛋白的研究现状、难点和策略.血浆是血液中无形的液体成分,是一种十分复杂和多样化的基质,包含数百万种蛋白质和小分子多肽、盐、类脂、氨基酸和糖等.血浆蛋白参与机体免疫、凝血-抗凝血、物质运输、营养和对生长信号调节等多种重要的生理功能.人体器官的病理变化可导致血浆蛋白在结构和数量上的改变,这种特征性的变化对疾病诊断和疗效监测具有十分重要的意义.然而,迄今为止人类对血浆蛋白的了解还十分有限,只有很少一部分血浆蛋白被用于常规的临床诊断.全面而系统地认识健康和疾病状态下血液循环中血浆蛋白的性质,会极大地加速对具有疾病诊断和治疗监测作用的血浆标志蛋白的研发.国际人类蛋白质组组织于2002年首先选择了血浆蛋白质组作为人类蛋白质组首期执行计划之一,其初期目标是：a.比较各种蛋白质组分析技术平台的优点和局限性;b.用这些技术平台分析人类血浆和血清的参考样本;c.建立人类血浆蛋白质组知识库.     

Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease

Background and Aims

Cystic Fibrosis associated liver disease (CFLD) develops in approximately 30% of CF patients. However, routine sensitive diagnostic tools for CFLD are lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CFLD.

Methods

45 CF patients were included in the study and received transient elastography. Differential regulation of 220 different serum proteins was assessed in a subgroup of patients with and without CFLD. Most interesting candidate proteins were further quantified and validated by ELISA in the whole patient cohort. To assess a potential relation of biomarker expression to the degree of hepatic fibrosis, serum biomarkers were further determined in 18 HCV patients where liver histology was available.

Results

43 serum proteins differed at least 2-fold in patients with CFLD compared to those without liver disease as identified in proteome profiling. In ELISA quantifications, TIMP-4 and Endoglin were significantly up-regulated in patients with CFLD as diagnosed by clinical guidelines or increased liver stiffness. Pentraxin-3 was significantly decreased in patients with CFLD. Serum TIMP-4 and Endoglin showed highest values in HCV patients with liver cirrhosis compared to those with fibrosis but without cirrhosis. At a cut-off value of 6.3 kPa, transient elastography compassed a very high diagnostic accuracy and specificity for the detection of CFLD. Among the biomarkers, TIMP-4 and Endoglin exhibited a high diagnostic accuracy for CFLD. Diagnostic sensitivities and negative predictive values were increased when elastography and TIMP-4 and Endoglin were combined for the detection of CFLD.

Conclusions

Serum TIMP-4 and Endoglin are increased in CFLD and their expression correlates with hepatic staging. Determination of TIMP-4 and Endoglin together with transient elastography can increase the sensitivity for the non-invasive diagnosis of CFLD.     

A Sampling of the Yeast Proteome

In this study, we examined yeast proteins by two-dimensional (2D) gel electrophoresis and gathered quantitative information from about 1,400 spots. We found that there is an enormous range of protein abundance and, for identified spots, a good correlation between protein abundance, mRNA abundance, and codon bias. For each molecule of well-translated mRNA, there were about 4,000 molecules of protein. The relative abundance of proteins was measured in glucose and ethanol media. Protein turnover was examined and found to be insignificant for abundant proteins. Some phosphoproteins were identified. The behavior of proteins in differential centrifugation experiments was examined. Such experiments with 2D gels can give a global view of the yeast proteome.     

激素型肾阳虚动物肝线粒体蛋白质组与能量代谢相关性

应用凝胶内差异显示电泳技术研究肾阳虚大鼠肝线粒体蛋白质组,并从肝线粒体蛋白质组角度阐述肾阳虚与能量代谢的关系.8个分别来自于肾阳虚大鼠和正常大鼠的肝线粒体蛋白质样品(各4个)分别用荧光染料Cy3、Cy5标记,以及8个样品等量混合物用Cy2标记作为内标,每一Cy3、Cy5标记样品与Cy2标记的内标等量混合后在同一胶中进行电泳分离,经不同光激发后扫描得到不同样品的蛋白质组图谱.经DeCyder软件结合内标分析,以肾阳虚组动物与正常组动物肝线粒体蛋白质相差1.2倍以上的蛋白作为差异蛋白,实验共获得16个差异蛋白质,经质谱测定和与蛋白质文库比对,鉴定11个蛋白质.其中,肾阳虚动物热休克蛋白60和70、肌氨酸脱氢酶、氨甲酰磷酸合成酶、亚硫酸盐氧化酶、ATP合酶、醛脱氢酶和NADH脱氢酶表达量增加,而丙酮酸脱氢酶、α酮戊二酸脱氢酶、脂酰辅酶A脱氢酶和鸟氨酸氨基转移酶表达量降低.实验表明,肾阳虚动物能量代谢相关酶的变化与肾阳虚的临床虚寒症状有关.     

Proteome analysis of Neisseria meningitidis serogroup A

Neisseria meningitidis is an encapsulated Gram-negative bacterium responsible for significant morbidity and mortality worldwide. Meningococci are opportunistic pathogens, carried in the nasopharynx of approximately 10% of asymptomatic adults. Occasionally they enter the bloodstream to cause septicaemia and meningitis. Meningococci are classified into serogroups on the basis of polysaccharide capsule diversity, and serogroup A strains have caused major epidemics mainly in the developing world. Here we describe a two-dimensional gel electrophoresis protein map of the serogroup A strain Z4970, a clinical isolate classified as ancestral to several pandemic waves. To our knowledge this is the first systematically annotated proteomic map for N. meningitidis. Total protein samples from bacteria grown on GC-agar were electrophoretically separated and protein species were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. We identified the products of 273 genes, covering several functional classes, including 94 proteins so far considered as hypothetical. We also describe several protein species encoded by genes reported by DNA microarray studies as being regulated in physiological conditions which are relevant to natural meningococcal pathogenicity. Since menA differs from other serogroups by having a fairly stable clonal population structure (i.e. with a low degree of variability), we envisaged comparative mapping as a useful tool for microevolution studies, in conjunction with established genotyping methods. As a proof of principle, we performed a comparative analysis on the B subunit of the meningococcal transferrin receptor, a vaccine candidate encoded by the tbpB gene, and a known marker of population diversity in meningococci. The results show that TbpB spot pattern variation observed in the maps of nine clinical isolates from diverse epidemic spreads, fits previous analyses based on allelic variations of the tbpB gene.     

A Human Proteome Detection and Quantitation Project

The lack of sensitive, specific, multiplexable assays for most human proteins is the major technical barrier impeding development of candidate biomarkers into clinically useful tests. Recent progress in mass spectrometry-based assays for proteotypic peptides, particularly those with specific affinity peptide enrichment, offers a systematic and economical path to comprehensive quantitative coverage of the human proteome. A complete suite of assays, e.g. two peptides from the protein product of each of the ∼20,500 human genes (here termed the human Proteome Detection and Quantitation project), would enable rapid and systematic verification of candidate biomarkers and lay a quantitative foundation for subsequent efforts to define the larger universe of splice variants, post-translational modifications, protein-protein interactions, and tissue localization.There is growing interest in the idea of a comprehensive Human Proteome Project (1) to exploit and extend the successful effort to sequence the human genome. Major challenges in defining a comprehensive Human Proteome Project (and distinguishing it from the genome effort) are 1) the potentially very large number of proteins with modified forms; 2) the diversity of technology platforms involved in their study; 3) the variety of overlapping biological “units” into which the proteome might be divided for organized conquest; and 4) sensitivity limitations in detecting proteins present in trace amounts. The process of analyzing and discussing these issues may (and ought to) be lengthy, as it addresses core scientific unknowns as well as decisions about the organization and scale of biomedical research in the future. The benefits of taking time to involve the entire biological research community, and especially the medical research segment, in these discussions are substantial.Progress in systematically measuring proteins, however, need not wait for the conclusion of such discussions. We propose a near-term tactical approach, called the human Proteome Detection and Quantitation (hPDQ)¹ project that will enable measurement of the human proteome in a way that would yield immediately useful results while the strategy for a comprehensive Human Proteome Project is worked out. The hPDQ project is aimed at overcoming present difficulties in answering basic biological questions about the relationship between protein abundance (or concentration) and gene expression, phenotype, disease, and treatment response; i.e., the growing field of protein biomarkers. It is thus focused on the study of biological variation affecting protein expression rather than study of structure and mechanism and in this initial form does not directly address splice variants or most post-translational modifications. It is aimed at providing immediately useful capabilities to the human biology research community, in a way that does not adversely impact funding for individual investigators and does not generate administrative constraints on their ability to set and change courses in the conduct of research. Specifically, the goal of the hPDQ is to enable individual biological researchers to measure defined collections of human proteins in biological samples with 1 ng/ml sensitivity and absolute specificity, at throughput and cost levels that permit the study of meaningfully large biological populations (∼500–5,000 samples).We clearly do not have this capability today. If an investigator defines a set of 20 proteins hypothesized to change in relation to some biological process or event, assays for only a minority (often none!) will typically be available. Further, these assays will lack absolute specificity and will not easily be multiplexed. Current proteomics research platforms are focused mainly on discovery; providing increasingly broad protein sampling surveys, generally at low throughput and high cost. Such approaches generally do not yield an economical or accurate measurement of a defined set of proteins in every sample. There is thus a fundamental barrier to hypothesis testing in quantitative proteomics, where relationships between protein abundance and biology are sought. A particularly important instance of this limitation occurs in the effort to establish useful biomarkers of disease, for diagnosis, for measuring efficacy of treatment, and for monitoring of disease recurrence. This limitation is largely responsible for the research community''s failure in recent years to bring forward significant numbers of new proteins as Food and Drug Administration approved diagnostic tests (2). However, if a robust, economical, and widely diffused capability to measure all human proteins existed, the research community would have the collective means to assess the utility of all human proteins as biomarkers in hundreds of diseases and other processes in the most efficient way.The need for new or improved biomarkers in many areas of healthcare has become critical. Early detection of cancer, coupled with surgical intervention, has the potential to radically improve survival (3), provided early markers exist and can be found. Without good biomarkers, degenerative diseases such as Alzheimer and chronic obstructive pulmonary disease (COPD) are difficult to detect early enough to benefit from the potential therapies. Clinical development of new drugs increasingly depends on identification of biomarkers for pharmacodynamic assessment of drug action to help guide dose and schedule, and predictive biomarkers for selection of patients who will benefit from therapy (4). Companion diagnostics are the currency of personalized medicine and represent those predictive or response biomarkers that are linked to specific therapeutics, substantially increasing their clinical value. Surrogate biomarkers (those biomarkers that substitute for a clinical outcome or response) are the most difficult to discover and to verify because of the long timeframe required but can radically shorten appropriate clinical trials. The impact of a vigorous increase in clinical biomarkers could thus be enormous, both in terms of patient well being and financial viability of healthcare systems worldwide.Protein measurements are also likely to play an important role in assessing the quality of material stored in large clinical sample collections (Biobanks). Much discussion has occurred recently regarding the value of banked samples because of unknown degrees of protein degradation occurring during acquisition, processing, and storage. This matter is of acute concern in the case of serum, where coagulation initiates a plethora of proteolytic cleavage events. The hPDQ may provide the opportunity to determine the value of each sample through the development of prototypic peptides tracking the stability of labile proteins.An attractive technology for achieving the objective of hPDQ is quantitative mass spectrometry, the sensitivity, and specificity of which are well established in the measurement of small molecules (5,6) and peptides (7,8). To achieve comprehensive quantitation of proteins, given the immense variability in their physical properties, these larger molecules are digested to component peptides using an enzyme such as trypsin, and protein amount is measured using proteotypic peptides (9,10) as specific stoichiometric surrogates. Multiple peptides from a target protein provide independent confirmation of this stoichiometry (equivalent to having multiple enzyme-linked immunosorbent assays with different antibody pairs), serving to control for the possibility of incomplete digestion or subsequent losses. Accurate calibration is achieved by spiking digested samples with known quantities of synthetic stable-isotope labeled peptides as internal standards (11,12). The sensitivity of this approach for multiplexed analysis of proteins in plasma has been extended from the microgram (13) to nanogram/ml levels by depletion of abundant proteins and limited peptide fractionation prior to analysis (14) or by capture of the subset of glycopeptides (15). Sensitivity and throughput of peptide MS measurements can be further increased to levels required in hPDQ by specific enrichment of the target peptides using anti-peptide antibodies. This method, called SISCAPA (for “stable isotope standards and capture by anti-peptide antibodies”) (16) or iMALDI (for immuno-MALDI) (17), combines the enhanced sensitivity of immunoassays with the specificity of mass spectrometry, while maintaining multiplexing capability. For these reasons we emphasize SISCAPA and iMALDI in this hPDQ proposal, although proteins in the 100 ng/ml or higher concentration are readily accessible by targeted MS in plasma without antibody enrichment. Combining these elements results in a measurement system, with the potential to measure 10–100 selected proteins at ng/ml levels in small (∼10 μl) samples of human plasma in a single short analytical run. Sensitivity can be further increased through the use of larger samples and/or advances in MS sensitivity. In comparison to the conventional ELISA approach, MS-based SISCAPA assays are less expensive to develop (one antibody instead of a carefully matched pair), easier to multiplex (off-target interactions being less likely with peptides than proteins), and provide absolute structural specificity (by reading the masses of multiple specific peptide fragments). This improved specificity solves a major problem plaguing clinical immunoassays for proteins such as thyroglobulin (18) and has led to the development of first clinical SISCAPA assay (19). In addition, since the mass spectrometer functions as a “second antibody” that identifies the captured peptides, the anti-peptide antibody used for peptide enrichment need not have perfect specificity. This greatly reduces the cost of affinity reagents, currently a limiting factor in developing ELISA assays for large numbers of protein analytes.Achieving the hPDQ goal by this approach would require that four resources be generally available. 1) A comprehensive database of proteotypic (protein-unique) peptides for each of the 21,500 human proteins (20), coupled with experimental or computational data identifying the best peptides for MS measurement and associated optimized MS instrument parameters. 2) At least two synthetic proteotypic peptides, labeled with stable isotope(s) and available in accurately quantitated aliquots, for use as internal measurement standards for quantitation of each protein. Such peptides are readily available today through custom order, at rapidly declining prices. 3) Anti-peptide antibodies specific for the same two proteotypic peptides per target protein, capable of binding the peptides with dissociation constants < 1e-9 (the level required in theory and practice to enrich low-abundance peptides from complex sample digests). Such antibodies are now being made for a variety of targets, and a robust production pipeline is being developed. Monoclonal antibodies would be preferred, despite their higher development cost, to establish a stable reagent supply, especially for those targets that prove useful as biomarkers. 4) Robust and affordable instrument platforms for quantitative analysis of small (amol to fmol) amounts of tryptic peptides and for sample preparation. Existing triple-quadrupole mass spectrometers (with a current worldwide installed base of more than 6,000 instruments) coupled with nanoflow (∼300–600 nl/min) liquid chromatography systems can meet this requirement and are undergoing rapid improvement with declining cost. MALDI platforms may provide similar capabilities at even higher throughput.We estimate that an initial pilot phase targeting 2,000 proteins selected for biomarker potential could be completed in two years at a cost of less than $50 million through funding of existing academic and commercial resources in a distributed network. In the following five years, the remaining 18,500 proteins could be targeted for $250 million, making use of anticipated technical improvements, particularly in the strategies for generating suitable high affinity monoclonal antibodies (21) in large numbers at low cost (22).Although the natural mechanism for providing the hPDQ database (resource 1 above) is through an academic collaboration, perhaps modeled on the successful Global Protein Machine (23) and Peptide Atlas (24) databases, the other resources would benefit from commercial distribution by experienced providers of instruments and reagents. The required instrument platforms (4 above) serve existing markets, and their further development is unlikely to require additional funding for hPDQ applications. However, business economics does not presently justify the expense of developing well characterized antibodies and peptides for quantitation of proteins that are not already recognized as pivotal in biological research (i.e. precisely those in need of the attention of the research community). Hence a substantial portion of the required funding for the proposed approach for such antibody and peptide reagents will be needed from government and philanthropic sources. A significant advantage of such diversified support would be the leverage it would provide in retaining in the public domain the identities of the selected peptides, their parameters and basic measurement protocols.The value of a general protein measurement capability for research is very substantial, but the proposed effort would not solve several larger issues that must await definition of a broader human proteome program. For example, the hPDQ project does not address the basic process of de novo proteome-wide discovery; the comprehensive exploration of splice forms, post-translational modifications, active fragments of preproteins or genetic variants (although once known, most of these can be targeted by the methods used here); interactions among proteins or with other molecules; or spatial arrangement of proteins in organs and tissues. Each of these areas would benefit from the resources proposed in hPDQ, but will likely require separate, coordinated large-scale efforts that are likely to identify additional sets of biomarkers. Thus although a complete suite of targeted assays is only a first step toward the complete human proteome, we feel that its fundamental importance for progress in biomarker research and its value as a foundation for protein quantitation justifies consideration as an initial step.In the beginning of the study of protein diagnostics, investigators at the Behring Institute discovered many of the well known plasma proteins and made associated specific antibodies and antibody-based quantitative tests available to the research community worldwide, spurring the initial round of plasma biomarker research. The application of monoclonal antibodies sparked additional discoveries through close coupling of protein “discovery” with simple quantitative monoclonal antibody-based assays - this “shortcut” to clinical measurement allowed investigators to publish more than 1,000 papers referring to the ovarian cancer marker CA125 (measured by ELISA) before the sequence of the protein was finally identified in 2001 (25). The broader proteomics technologies (beginning with the two-dimensional electrophoresis technology that formed the basis of the Human Protein Index Project (26) formulated by two of us almost 30 years ago, and extending to modern shotgun-style MS-based approaches) have radically expanded the universe of observable proteins. However, quantitative specific assay capabilities have not kept pace with this expansion, leading to the current gap between biomarker proteomics and clinical biomarker output. It is now time to address this gap and realize the benefits of a clinically accessible human proteome. Effective translation of basic research into tangible medical benefit requires it.     

The Human Liver Proteome Project (HLPP) workshop during the 4th HUPO World Congress

The Human Liver Proteome Project (HLPP) is the first initiative of the Human Proteome Organisation (HUPO) to target a human organ/tissue and aims at the establishment of a biological atlas of the liver to advance our understanding of liver functions and to provide the tools to develop new diagnostics and therapeutics for liver diseases. The major achievements of HLPP during its pilot phase (2003-2005) were presented during a one-day workshop held on August 27, 2005, immediately prior to the 4th HUPO World Congress in Munich, Germany. These include (i) the participation of a large number of laboratories worldwide and the initiation of international research collaborations; (ii) the establishment of a management infrastructure and (iii) the development of standard operating procedures and the generation and collection of a first set of expression profile data. A summary of the workshop was subsequently presented by Professor Fuchu He, the Chair of this initiative, during the HUPO 4th Annual World Congress.     

The 2009 Human Liver Proteome Project (HLPP) Workshop 26 September 2009, Toronto,Canada

The Human Liver Proteome Project (HLPP) was formally launched by HUPO in 2002. The 11th HLPP Workshop was held on September 26th, 2009 during the 8th HUPO World Congress in Toronto, Canada. The representative progresses were presented from four groups. Subsequently, the workshop ended with a lively discussion on four topics related to the project as well as other initiatives.     

The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study

Objectives

Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS.

Methods

The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9–10 pr. groups).

Results

The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD.

Conclusion

The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.     

The Redox Proteome

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges.     

The 2011 Human Liver Proteome Project (HLPP) Workshop September 5, 2011, Geneva, Switzerland

During the 10th HUPO Annual World Congress held in Geneva (Switzerland) from 4th to 7th September, a workshop on Human Liver Proteome Project (HLPP) Initiative took place. Four research groups presented their latest results from different ongoing projects. Later on, during the HLPP executive members' meeting, the status of current projects and the next possible steps to be taken were discussed.