The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent.
HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection.
Tsuji
Takahiro
T
Centre for Research in Infectious Disease, School of Medicine & Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Sheehy
Noreen
N
Gautier
Virginie W
VW
Hayakawa
Hitoshi
H
Sawa
Hirofumi
H
Hall
William W
WW
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002472:Cell Transformation, Viral / Q000235:genetics; D002522:Chlorocebus aethiops; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism
D016356:Gene Products, tax; D028861:Nuclear Pore Complex Proteins; D051996:Transcription Factor RelA; D028961:beta Karyopherins