Abstract |
The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability.
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Authors | Shuichi Kusano, Makoto Yoshimitsu, Miho Hachiman, Masanori Ikeda |
Journal | Virology
(Virology)
Vol. 486
Pg. 219-27
(Dec 2015)
ISSN: 1096-0341 [Electronic] United States |
PMID | 26469549
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Gene Products, tax
- MDFIC protein, human
- Myogenic Regulatory Factors
- NF-kappa B
- tax protein, Human T-lymphotrophic virus 1
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Topics |
- Gene Expression Regulation, Viral
- Gene Products, tax
(genetics, metabolism)
- HTLV-I Infections
(genetics, metabolism, virology)
- Host-Pathogen Interactions
- Human T-lymphotropic virus 1
(genetics, metabolism)
- Humans
- Myogenic Regulatory Factors
(genetics, metabolism)
- NF-kappa B
(genetics, metabolism)
- Protein Binding
- Proteolysis
- Terminal Repeat Sequences
- Transcriptional Activation
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