C. Beraud et Wc. Greene, INTERACTION OF HTLV-I TAX WITH THE HUMAN PROTEASOME - IMPLICATIONS FOR NF-KAPPA-B INDUCTION, Journal of acquired immune deficiency syndromes and human retrovirology, 13, 1996, pp. 76-84
The human T-cell leukemia virus type I (HTLV-I) has been etiologically
associated with the development of the adult T-cell leukemia (ATL) as
well as a degenerative neurologic syndrome termed tropical spastic pa
raparesis (TSP). HTLV-I encodes a potent transactivator protein termed
Tax that appears to play an important I-olein the process of T-cell i
mmortalization. Even though the mechanisms by which Tax induces transf
ormation are still unknown, it seems likely that the ability of Tax to
alter the expression of many cellular genes plays an important part i
n this process. Tax does not bind directly to DNA but rather deregulat
es the activity of cellular transcription factors. One family of host
transcription factors whose activity is altered by Tax includes NF-kap
pa B/Rel. These transcription factors are post-transcriptionally regul
ated by their assembly with a second family of inhibitory proteins ter
med I kappa B that serve to sequester the NF-kappa B/Rel complexes in
the cytoplasm. Upon cellular activation, I kappa B alpha is phosphoryl
ated, polyubiquitinated, and degraded in the proteasome. This proteoly
tic event liberates NF-kappa B, permitting its rapid translocation int
o the nucleus where it binds to its cognate enhancer elements. Similar
ly, the p105 precursor of the NF-kappa B p50 subunit Is also post-tran
slationally processed in the proteasome. The mechanisms by which Tax a
ctivates NF-kappa B remain unclear, and Findings presented in the lite
rature are often controversial. We identified a physical interaction b
etween Tax and the HsN3 subunit of the human proteasome. This raises t
he intriguing possibility that physical association of the HsN3 protea
some subunit with HTLV-I Tax coupled with the independent interaction
of Tax with either p100 or p65-I kappa B alpha targets these cytoplasm
ic NF-kappa B/Rel complexes to the proteasome far processing.