Sk. Woo et al., Nuclear redistribution of tonicity-responsive enhancer binding protein requires proteasome activity, AM J P-CELL, 278(2), 2000, pp. C323-C330
Tonicity-responsive enhancer binding protein (To-nEBP) is the transcription
factor that regulates tonicity-responsive expression of the genes for the
sodium-myoinositol cotransporter (SMIT) and the sodium-chloride-betaine cot
ransporter (BGT1). Hypertonicity stimulates the activity of TonEBP due to a
combination of increased protein abundance and increased nuclear distribut
ion (proportion of TonEBP that is in the nucleus). We found that inhibitors
of proteasome activity markedly reduce the induction of SMIT and BGT1 mRNA
in response to hypertonicity. These inhibitors also reduce hypertonicity-i
nduced stimulation of expression of a reporter gene controlled by the tonic
ity-responsive enhancer. Western and immunohistochemical analyses revealed
that the proteasome inhibitors reduce the hypertonicity-induced increase of
TonEBP in the nucleus by inhibiting its nuclear redistribution without aff
ecting its abundance. Although the nuclear distribution of TonEBP is sensit
ive to inhibition of proteasome activity as is that of nuclear factor (NF)-
kappa B, the signaling pathways appear to be different in that hypertonicit
y does not affect the nuclear distribution of NF-kappa B. Conversely, treat
ment with tumor necrosis factor-alpha increases the nuclear distribution of
NF-kappa B but not TonEBP.