I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions.

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.

• 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)
• 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

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