Regulation of Nrf2 transactivation domain activity by p160 RAC3/SRC3 and other nuclear co-regulators

Wen Lin, Guoxiang Shen, Xiaoling Yuan, Mohit R. Jain, Siwang Yu, Aihua Zhang, J. Don Chen, Ah Ng Tony Kong

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of Phase II detoxifying enzymes and antioxidant enzymes in response to many cancer chemopreventive compounds. In this study, we investigated the role of receptor associated coactivator (RAC3) or steroid receptor coactivator-3 (SRC3) and other nuclear co-regulators including CBP/p300 (CREB-binding protein), CARM1 (Coactivator-associated arginine methyltransferase), PRMT1 (Protein arginine methyl-transferase 1), and p/CAF (p300/ CBP-associated factor) in the transcriptional activation of a chimeric Gal4-Nrf2-Luciferase system containing the transactivation domain (TAD) of Nrf2 in HepG2 cells. The results indicated that RAC3 up-regulated the transactivation activity of Gal4-Nrf2-(1-370) in a dose-dependent manner. The enhancement of transactivation domain activity of Gal4-Nrf2-(1-370) by RAC3 was dampened in the presence of dominant negative mutants of RAC3. Next we studied the effects of other nuclear co-regulators including CBP/ p300, CARM1, PRMT1 and p/CAF, and the results showed that they had different level of positive effects on this transactivation domain activity of Gal4-Nrf2-(1-370). But importantly, synergistic effects of these co-regulators in the presence of RAC3/SRC3 on the transactivation activity of Gal4-Nrf2-(1-370) were observed. In summary, our present study showed for the first time that the 160 RAC3/SRC3 is involved in the functional transactivation of TAD of Nrf2 and that the other nuclear co-regulators such as CBP/p300, CARM1, PRMT1 and p/CAF can also transcriptionally activate this TAD of Nrf2 and that they could further enhance the transactivation activity mediated by RAC3/SRC3.

Original languageEnglish (US)
Pages (from-to)304-310
Number of pages7
JournalJournal of Biochemistry and Molecular Biology
Volume39
Issue number3
DOIs
StatePublished - 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Keywords

  • CARM1
  • CBP/p300
  • Nrf2
  • PRMT1
  • RAC3/SRC3
  • p/CAF

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