The Network Organization of Cancer-associated Protein Complexes in Human Tissues

Zhao, Jing; Lee, Sang Hoon; Huss, Mikael; Holme, Petter

doi:10.1038/srep01583

Cited by 38 publications

(18 citation statements)

References 50 publications

(61 reference statements)

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“…55 To investigate whether Mtp-proteins prefer to form complexes or whether complex-forming proteins prefer to be post-translationally modified, we analyzed 1845 human complexes, comprising 8842 components, retrieved from the CORUM database (Comprehensive Resource of Mammalian Protein Complexes 56 ). Among all components, 7173 (92%) of them were proteins with PTM sites.…”

Section: Exploratory Analysis On Mtp-proteins: Mtp-proteins Are Enricmentioning

confidence: 99%

Human Proteins with Target Sites of Multiple Post-Translational Modification Types Are More Prone to Be Involved in Disease

et al. 2014

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Many proteins can be modified by multiple types of post-translational modifications (Mtp-proteins). Although some post-translational modifications (PTMs) have recently been found to be associated with life-threatening diseases like cancers and neurodegenerative disorders, the underlying mechanisms remain enigmatic to date. In this study, we examined the relationship of human Mtp-proteins and disease and systematically characterized features of these proteins. Our results indicated that Mtp-proteins are significantly more inclined to participate in disease than proteins carrying no known PTM sites. Mtp-proteins were found significantly enriched in protein complexes, having more protein partners and preferred to act as hubs/superhubs in protein-protein interaction (PPI) networks. They possess a distinct functional focus, such as chromatin assembly or disassembly, and reside in biased, multiple subcellular localizations. Moreover, most Mtp-proteins harbor more intrinsically disordered regions than the others. Mtp-proteins carrying PTM types biased toward locating in the ordered regions were mainly related to protein-DNA complex assembly. Examination of the energetic effects of PTMs on the stability of PPI revealed that only a small fraction of single PTM events influence the binding energy of >2 kcal/mol, whereas the binding energy can change dramatically by combinations of multiple PTM types. Our work not only expands the understanding of Mtp-proteins but also discloses the potential ability of Mtp-proteins to act as key elements in disease development.

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Section: Exploratory Analysis On Mtp-proteins: Mtp-proteins Are Enricmentioning

confidence: 99%

Human Proteins with Target Sites of Multiple Post-Translational Modification Types Are More Prone to Be Involved in Disease

et al. 2014

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“…It has been reported that certain proteins are cancer-associated [ 45 , 46 ]. Therefore, identifying the common proteins presented by cancer cells and investigating their relevance to cancers may provide clues about cancer development.…”

Section: Resultsmentioning

confidence: 99%

Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX

Teng

Zhang

et al. 2015

PLoS ONE

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Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment), have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

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“…One of the challenges in constructing accurate CCIs networks is the lack of sufficient structural information, which can resolve the availability of protein interaction-bindings site interfaces. Although there is an increasing amount of 3D structures of protein complexes being deposited into the protein data bank (PDB) [87], the coverage is still very sparse Human [169,170] across all proteomes, including human [88]. Using the protein interaction networks as they exist currently, it is unknown whether a hub protein, with many interactions in the network, uses single or multiple-binding site interfaces.…”

Section: Understanding the Network Organization And Structure Of Compmentioning

confidence: 99%

From proteomes to complexomes in the era of systems biology

Clancy

Hovig

2014

Proteomics

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Protein complexes carry out almost the entire signaling and functional processes in the cell. The protein complex complement of a cell, and its network of complex-complex interactions, is referred to here as the complexome. Computational methods to predict protein complexes from proteomics data, resulting in network representations of complexomes, have recently being developed. In addition, key advances have been made toward understanding the network and structural organization of complexomes. We review these bioinformatics advances, and their discovery-potential, as well as the merits of integrating proteomics data with emerging methods in systems biology to study protein complex signaling. It is envisioned that improved integration of proteomics and systems biology, incorporating the dynamics of protein complexes in space and time, may lead to more predictive models of cell signaling networks for effective modulation.

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The Network Organization of Cancer-associated Protein Complexes in Human Tissues

Cited by 38 publications

References 50 publications

Human Proteins with Target Sites of Multiple Post-Translational Modification Types Are More Prone to Be Involved in Disease

Human Proteins with Target Sites of Multiple Post-Translational Modification Types Are More Prone to Be Involved in Disease

Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX

From proteomes to complexomes in the era of systems biology

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