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- Title
NRP/B mutations impair Nrf2-dependent NQO1 induction in human primary brain tumors.
- Authors
Seng, S.; Avraham, H. K.; Birrane, G.; Jiang, S.; Li, H.; Katz, G.; Bass, C. E.; Zagozdzon, R.; Avraham, S.
- Abstract
Brain tumors are associated with genetic alterations of oncogenes and tumor suppressor genes. Accumulation of reactive oxygen species (ROS) in cells leads to oxidative stress-induced damage, resulting in tumorigenesis. Here, we showed that the nuclear matrix protein nuclear restricted protein in brain (NRP/B) was colocalized and interacted with NF-E2-related factor 2 (Nrf2). During oxidative stress response, NRP/B expression and its interaction with Nrf2 were upregulated in SH-SY5Y cells. Association of NRP/B with Nrf2 was crucial for NAD(P)H:quinone oxidoreductase 1 (NQO1) expression. NRP/B was localized predominantly in the nucleus of normal brain cells, whereas in primary brain tumors NRP/B was almost exclusively contained in the cytoplasm. In addition, unlike wild-type NRP/B, the expression of NRP/B mutants isolated from primary brain tumors was found in the cytoplasm, and these mutants failed to induce Nrf2-dependent NQO1 transcription. Thus, NRP/B mutations and their altered localization resulted in changes in NRP/B function and deregulation of Nrf2-dependent NQO1 activation in brain tumors. This study provides insights into the mechanism by which the NRP/B modulates Nrf2-dependent NQO1 induction in cellular protection against ROS in brain tumors.Oncogene (2009) 28, 378–389; doi:10.1038/onc.2008.396; published online 3 November 2008
- Subjects
BRAIN tumor genetics; ONCOGENES; TUMOR suppressor genes; REACTIVE oxygen species; OXIDATIVE stress; CARCINOGENESIS; NUCLEAR matrix; OXIDOREDUCTASES
- Publication
Oncogene, 2009, Vol 28, Issue 3, p378
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2008.396