Specific interaction of HTLV tax protein and a human type IV neuronal intermediate filament protein.
The human T-cell leukemia virus (HTLV) is associated with adult T cell leukemia and neurological disorders (TSP/HAM). The HTLV transcriptional transactivator, Tax, is known to exert its effect through protein-protein interaction with several transcription factors that activate genes in T cell proliferation. The pathogenic mechanism in the CNS is less defined. Using the yeast two-hybrid system, we have identified a specific Tax-binding protein as the neuronal specific intermediate filament protein, alpha-internexin. Tax binds to the domain corresponding to the rod region of alpha-internexin, which is essential for neurofilament assembly. The Tax domains involved in binding are separable from those involved in transactivation. TxBP-1/alpha-internexin and Tax are expressed in the cytoplasm and nucleus, respectively, when expressed alone, but in coexpressing cells, colocalization of both proteins was observed in a perinuclear, punctate distribution. This in vivo interaction also resulted in a dramatic reduction in Tax transactivation and the network formation by alpha-internexin. The specific interaction of Tax and a neuronal specific intermediate filament protein may provide a clue to the pathogenesis of TSP/HAM.
Reddy
T R
TR
Department of Medicine, University of California at San Diego, La Jolla 92093-0665, USA.
Li
X
X
Jones
Y
Y
Ellisman
M H
MH
Ching
G Y
GY
Liem
R K
RK
Wong-Staal
F
F
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D016415:Sequence Alignment
D002352:Carrier Proteins; D016356:Gene Products, tax; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C046643:alpha-internexin