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  • Meeting abstract
  • Open Access

HTLV-1 bZIP factor enhances TGF-beta signaling through p300 coactivator

  • 1,
  • 1,
  • 1,
  • 2,
  • 3, 4, 5 and
  • 1Email author
Retrovirology20118 (Suppl 1) :A142

https://doi.org/10.1186/1742-4690-8-S1-A142

  • Published:

Keywords

  • 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.

Authors’ Affiliations

(1)
Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan
(2)
Center for Retrovirus Research and Departments of Veterinary Biosciences and Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA
(3)
Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
(4)
Division of Biochemistry, the Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
(5)
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi-shi, Saitama 332-0012, Japan

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