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Title: Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enrichedmore » through modular analysis. • Tissue- and time-specific pathways were identified.« less
Authors:
 [1] ;  [2] ; ;  [1] ; ;  [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [2]
  1. Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)
  2. (China)
  3. Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China)
Publication Date:
OSTI Identifier:
22465703
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 283; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; BIOLOGICAL EFFECTS; CARCINOGENS; GENES; HUMAN POPULATIONS; INFECTIOUS DISEASES; INTERACTIONS; LIVER; LUNGS; NEOPLASMS; POLLUTANTS; PROTEINS; PYRENE; SIGNALS; TOPOLOGY