- Meeting abstract
- Open Access
HTLV-1 bZIP factor enhances TGF-beta signaling through p300 coactivator
© Zhao et al; licensee BioMed Central Ltd. 2011
- Published: 6 June 2011
- Virus Type
- Signaling Activation
- Ternary Complex
- Leukemia Virus
- Physiological Level
Adult T-cell leukemia (ATL) is a neoplastic disease caused by Human T-cell leukemia virus type 1 (HTLV-1). ATL cells possess a CD4+CD25+ phenotype, similar to that of regulatory T cells (Treg). The HTLV-1 bZIP factor (HBZ), which is consistently expressed in ATL, has a critical role in the development of ATL and HAM/TSP. In the present study, we found that HBZ enhanced TGF-beta/Smad transcriptional activity in a manner dependent on p300. Co-immunoprecipitation assay confirmed that HBZ interacted with Smad3, and formed a ternary complex with Smad3 and p300. In the presence of HBZ, the interaction between Smad3 and p300 was enhanced. The N-terminal LXXLL motif of HBZ was essential for HBZ-mediated TGF-beta signaling activation, while Smad3 interacted with HBZ through its C-terminal MH2 domain. Furthermore, physiological level of HBZ could rescue the repressed TGF-beta responses by Tax. We also found that HBZ activated transcription of the Foxp3 gene through its Smad site. Our study shows that HBZ enhances TGF-beta signaling while Tax suppresses this pathway, and this enhancing activity leads to transcription of Foxp3 gene.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.