Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases
Orange, blue and grey nodes denote tissue-specific, globally-expressed, and other proteins, respectively; diamond nodes mark hereditary disease genes; edges denote PPIs. A. BRCA1 is a globally-expressed tumor-suppressor hub, and ESR1 is an estrogen receptor protein that activates cellular proliferation. The breast-specific PPI linking BRCA1 and ESR1 provides a potential basis for the breast-specific effects of BRCA1 germline mutations . B. A lung-specific PPI connects the widely-expressed epidermal growth factor receptor EGFR and its ligand protein epiregulin (EREG). Germline mutations in EGFR lead to lung cancer , and EREG was shown to confer invasive properties in an EGFR-dependent manner . C. Muscle-specific PPIs connect the widely expressed trans-membrane cell adhesion receptor dystroglycan 1 (DAG1) to its muscle-specific ligand dystrophin (DMD), and to caveolin 3 (CAV3) which regulates DMD by preventing the DAG1-DMD PPI. Mutations in all three genes give rise to various forms of muscular dystrophies. D. The brain-specific PPIs that link members of the globally-expressed protein complex EIF2B to the netrin-1-receptor DCC may underlie the brain-specific effects of germline mutations in EIF2B complex members .