RGD Reference Report - HBP1 repression of the p47phox gene: cell cycle regulation via the NADPH oxidase. - Rat Genome Database

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HBP1 repression of the p47phox gene: cell cycle regulation via the NADPH oxidase.

Authors: Berasi, Stephen P  Xiu, Mei  Yee, Amy S  Paulson, K Eric 
Citation: Berasi SP, etal., Mol Cell Biol. 2004 Apr;24(7):3011-24.
RGD ID: 12911006
Pubmed: PMID:15024088   (View Abstract at PubMed)
PMCID: PMC371097   (View Article at PubMed Central)

Several studies have linked the production of reactive oxygen species (ROS) by the NADPH oxidase to cellular growth control. In many cases, activation of the NADPH oxidase and subsequent ROS generation is required for growth factor signaling and mitogenesis in nonimmune cells. In this study, we demonstrate that the transcriptional repressor HBP1 (HMG box-containing protein 1) regulates the gene for the p47phox regulatory subunit of the NADPH oxidase. HBP1 represses growth regulatory genes (e.g., N-Myc, c-Myc, and cyclin D1) and is an inhibitor of G(1) progression. The promoter of the p47phox gene contains six tandem high-affinity HBP1 DNA-binding elements at positions -1243 to -1318 bp from the transcriptional start site which were required for repression. Furthermore, HBP1 repressed the expression of the endogenous p47phox gene through sequence-specific binding. With HBP1 expression and the subsequent reduction in p47phox gene expression, intracellular superoxide production was correspondingly reduced. Using both the wild type and a dominant-negative mutant of HBP1, we demonstrated that the repression of superoxide production through the NADPH oxidase contributed to the observed cell cycle inhibition by HBP1. Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene. This study defines a transcriptional mechanism for regulating intracellular ROS levels and has implications in cell cycle regulation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of transcription by RNA polymerase II involved_inIDA 12911006PMID:15024088NTNU_SB 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Hbp1  (HMG-box transcription factor 1)


Additional Information