Kl. Jordan-sciutto et al., Fetal Alz-50 clone 1 (FAC1) protein interacts with the myc-associated zincfinger protein (ZF87/MAZ) and alters its transcriptional activity, BIOCHEM, 39(12), 2000, pp. 3206-3215
Transcription factors mediate their regulatory effects through interaction
with DNA and numerous nuclear proteins. The fetal Alz-50 clone 1 (FAC1) pro
tein, a novel DNA-binding protein with the capacity to repress transcriptio
n, is likely to function through a similar mechanism (I), Using the two-hyb
rid yeast screen, we have shown that FAC1 interacts with the myc-associated
zinc finger protein (ZF87/MAZ), This association was confirmed in vitro wi
th recombinant protein. The ZF87/MAZ interaction domain was mapped to the r
egion containing a putative nuclear localization signal (NLS) and nuclear e
xport sequence (NES) of FAC1, using deletion mutants of the FAC1 protein. F
AC1, on the other hand, recognizes a conformational interface that includes
the proline/alanine-rich domain of ZF87/MAZ and the first zinc finger. Cot
ransfection of NIH3T3 cells with ZF87/MAZ and a luciferase reporter contain
ing the SV40 promoter and enhancer results in an increase in transcriptiona
l activation, suggesting ZF87/MAZ is able to recognize its consensus bindin
g site present in the SV40 promoter. Cotransfection with FAC1 reduces the l
evel of ZF87/MAZ-induced activation of the SV40 promoter in a dose dependen
t manner. A mutant FAC1, lacking the ZF87/MAZ interaction domain, does not
alter ZF87/MAZ activation of the SV40 promoter. These data demonstrate that
interaction between FAC1 and ZF87/MAZ alters the transactivation capacity
of ZF87/MAZ. By immunoblot analysis, FAC1 and ZF87/MAZ exhibit similar tiss
ue distribution and co-localize to pathologic structures in Alzheimer's dis
ease brain. Coexpression of FAC1 and ZF87/MAZ suggest that interaction of t
hese two proteins will have biological implications for gene regulation in
neurodegeneration.