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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#_4 http://www.w3.org/ns/prov#value 2.3.2. p47 phox, reactive oxygen species, and growth factor signaling. Using a high-affinity HBP1 binding site, we scanned databases for new possible target genes that might illuminate the role of HBP1 in G1 progression and in tumor suppression. From this initial database search, the p47 phox gene was identified. The p47 phox gene encodes a subunit of the NADPH oxidase, which has emerged as an integral component of mitogenic pathways [Berasi, 2004 #885]. 2.3.2.1. Cell cycle and cancer implications As shown in Fig. 5, the NADPH oxidase catalyzes the one electron reduction of O2 to O2 (superoxide) with NADPH as the electron donor. The NADPH oxidase is the principle source of intracellular reactive oxygen species (ROS) that is generated by mitogenic signaling. The p47phox gene is a regulatory subunit for the NADPH oxidase complex. The general configuration of the NADPH oxidase complex consists of ubiquitous cytoplasmic regulatory subunits (e.g., p47phox) that combine with a membrane complex that includes a tissue-specific gp91phox catalytic subunits (sometimes denoted NOX; reviewed in (Cheng et al., 2001). The assembly of regulatory and catalytic components generates the active NADPH oxidase complex. The importance of a functional NADPH oxidase is underscored by the observation that mutations of the p47phox and gp91phox genes are associated with chronic granulomatosis, in which patients have increased susceptibility to bacterial and fungal infections (reviewed in Cheng et al., 2001). In these patients, the mutations in p47 phox and gp91 phox compromise NADPH oxidase activity. Unlike the tissue-specific catalytic subunits, the regulatory and cytoplasmic components are largely ubiquitous. For example, the expression of the same p47phox/NCF1 gene occurs in most cell types (reviewed in Cheng et al., 2001). For non-immune cells, the regulation of NADPH oxidase activity and of intracellular ROS levels dictate the efficacy of signaling networks involved in cancer (reviewed in Xu et al., 2002 and Finkel, 2003). Mitogenic stimulation with growth factors (e.g., EGF, PDGF, etc.) in non-immune cells requires ROS that is generated from the NADPH oxidase complex (reviewed in Sauer et al., 2001). Recent studies have highlighted a key role for ROS in modulating signaling networks through reversible cysteine oxidation in the control of tyrosine phosphatase activity (Meng et al., 2002 and Nimnual et al., 2003); reviewed in Xu et al., 2002). NADPH oxidase activity and ROS levels also have an integral role in signaling that is regulated by the small G-proteins RAS and RAC (Irani et al., 1997 and Joneson and Bar-Sagi, 1998). Stable transfection of NIH/3T3 fibroblasts with active Ras (H-RasV12) results in transformation and in significant intracellular ROS generation. http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15225871 http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15225871 http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#_4 http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg#pubinfo http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg http://purl.org/dc/terms/created 2014-07-03T14:30:25.326+02:00 http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAd24C4bZOOani7q1RrCcsC4GCtUFId60q6SD7u0Wbidg http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234