Zinc is essential for human health, and its deficiency in human beings resu
lts In growth failure, immune disorders affecting Th1 functions, decreased
interleukin-2 (IL-2) production, and cognitive impairment. Nearly 2000 tran
scription factors require zinc for their structural integrity; however, it
is not known whether cellular zinc deficiency results in any change in acti
vation of any of the transcription factors. Inasmuch as NF-kappaB binds to
the promoter enhancer area of IL-2 and IL-2R alpha genes, we investigated t
he effect of zinc deficiency on activation of NF-kappaB and its binding to
DNA in HUT-78, a Th0 malignant human lymphoblastoid cell line. We show here
for the first time that in zinc-deficient HUT-78 cells, phosphorylated I k
appaB, and IKK, ubiquitinated I kappaB and binding of NF-kappaB to DNA were
all significantly decreased. Zinc increased the translocation of NF-kappaB
from cytosol to nucleus. We also demonstrate that the binding of recombina
nt NF-kappaB (p50)(2) to DNA in HUT-78 cells was zinc specific. We conclude
that zinc plays an important role in the activation of NF-kappaB in HUT-78
cells.