P. Yalamanchili et al., INHIBITION OF HOST-CELL TRANSCRIPTION BY POLIOVIRUS - CLEAVAGE OF TRANSCRIPTION FACTOR CREB BY POLIOVIRUS-ENCODED PROTEASE 3C(PRO), Journal of virology, 71(2), 1997, pp. 1220-1226
Host cell RNA polymerase II-mediated transcription is inhibited by pol
iovirus infection, Previous studies from our laboratory showed that ac
tivated transcription from a cyclic AMP-responsive element (CRE)-conta
ining promoter was severely inhibited in extracts prepared from poliov
irus-infected HeLa cells compared to those from mock-infected cells. H
ere we demonstrate that the CRE-binding protein, CREB, is specifically
cleaved by the poliovirus encoded protease 3C(pro) both in vitro and
in virus-infected cells. The proteolytic cleavage of CREB leads to a s
ignificant loss of its DNA binding as well as transcriptional activity
, Additionally, we demonstrate that the phosphorylated, transcriptiona
lly active form of CREB is cleaved by the viral protease in vitro. The
results presented here suggest that a direct cleavage of CREB by the
viral protease 3C(pro) leads to inhibition of CREB-activated transcrip
tion in poliovirus-infected HeLa cells.