Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity.
The primary function of the HIV-1 regulatory protein Tat, activation of transcription from the viral LTR, is highly regulated by complex interactions between Tat and a number of host cell proteins. Tat nuclear import, a process mediated by importin beta, is a prerequisite for its activity. Here, we report and characterize the interaction of the human inhibitor of MyoD family domain-containing protein (I-mfa), HIC, with Tat at a biochemical and a functional level. This interaction was shown to occur in vivo and in vitro and to involve the nuclear localization signal and the transactivation responsive element-binding domains of Tat and the I-mfa domain of HIC. Coexpression of HIC and Tat resulted in the down-regulation of transactivation of the HIV-1 LTR, and colocalization studies revealed the cytoplasmic sequestration of Tat by HIC. Functionally this sequestration appears to be the underlying mechanism of LTR transcriptional repression by HIC and represents a unique mechanism for the control of Tat activity and regulation of HIV-1 replication.
Gautier
Virginie W
VW
Department of Medical Microbiology, Centre for Research in Infectious Diseases, Conway Institute of Molecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Sheehy
Noreen
N
Duffy
Margaret
M
Hashimoto
Kenichi
K
Hall
William W
WW
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D015536:Down-Regulation; D015696:Gene Products, tat / Q000032:analysis / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000032:analysis / Q000378:metabolism*; D019913:Nuclear Localization Signals; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; C478034:MDFIC protein, human; D018006:Myogenic Regulatory Factors; D019913:Nuclear Localization Signals; D054322:tat Gene Products, Human Immunodeficiency Virus