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- Title
NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx.
- Authors
Bui-Nguyen, T. M.; Pakala, S. B.; Sirigiri, R. D.; Xia, W.; Hung, M.-C.; Sarin, S. K.; Kumar, V.; Slagle, B. L.; Kumar, R.
- Abstract
Metastasis-associated protein 1 (MTA1), a master chromatin modifier, has been shown to regulate cancer progression and is widely upregulated in human cancer, including hepatitis B virus-associated hepatocellular carcinomas (HCCs). Here we provide evidence that hepatitis B virus transactivator protein HBx stimulates the expression of MTA1 but not of MTA2 or MTA3. The underlying mechanism of HBx stimulation of MTA1 involves HBx targeting of transcription factor nuclear factor (NF)-κB and the recruitment of HBx/p65 complex to the NF-κB consensus motif on the relaxed MTA1 gene chromatin. We also discovered that MTA1 depletion in HBx-expressing cells severely impairs the ability of HBx to stimulate NF-κB signaling and the expression of target proinflammatory molecules. Furthermore, the presence of HBx in HBx-infected HCCs correlated well with increased MTA1 and NF-κB-p65. Collectively, these findings revealed a previously unrecognized integral role of MTA1 in HBx stimulation of NF-κB signaling and consequently, the expression of NF-κB targets gene products with functions in inflammation and tumorigenesis.
- Subjects
HEPATITIS B virus; CHROMOSOMES; TRANSCRIPTION factors; CANCER invasiveness; LIVER cancer; LIVER diseases
- Publication
Oncogene, 2010, Vol 29, Issue 8, p1179
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2009.404