TY - JOUR
T1 - Direct suppression of Stat1 function during adenoviral infection
AU - Look, Dwight C.
AU - Roswit, William T.
AU - Frick, Annette G.
AU - Gris-Alevy, Yael
AU - Dickhaus, Dellice M.
AU - Walter, Michael J.
AU - Holtzman, Michael J.
N1 - Funding Information:
The authors gratefully acknowledge S. Brody, J. Darnell, Jr., A. Deisseroth, R. Di Lauro, M. Dustin, W. Greene, P. Gunning, S. Hollenberg, Y. Henderson, T. Ley, E. Moran, E. Ruoslahti, D. Staunton, and S. Weintraub for generous gifts of reagents and M. Pelletier, M. Taguchi, and R. Tidwell for technical assistance. This research was supported by grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Martin Schaefer Fund, and the Alan A. and Edith L. Wolff Charitable Trust.
PY - 1998/12
Y1 - 1998/12
N2 - The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription (STAT) proteins. However, we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 (via E1A N-terminal and Stat1 C-terminal residues) and block IFNγ-driven, Stat1-dependent gene activation and consequent function during early-phase infection in the natural host cell. The results provide a distinct and more specific mechanism for E1A-mediated immune suppression and an alternative model of IFNγ-driven enhanceosome formation that may allow for other adaptors (in addition to p300/CBP) to link Stat1 to the basal transcription complex.
AB - The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription (STAT) proteins. However, we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 (via E1A N-terminal and Stat1 C-terminal residues) and block IFNγ-driven, Stat1-dependent gene activation and consequent function during early-phase infection in the natural host cell. The results provide a distinct and more specific mechanism for E1A-mediated immune suppression and an alternative model of IFNγ-driven enhanceosome formation that may allow for other adaptors (in addition to p300/CBP) to link Stat1 to the basal transcription complex.
UR - http://www.scopus.com/inward/record.url?scp=0032432076&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80652-4
DO - 10.1016/S1074-7613(00)80652-4
M3 - Article
C2 - 9881977
AN - SCOPUS:0032432076
SN - 1074-7613
VL - 9
SP - 871
EP - 880
JO - Immunity
JF - Immunity
IS - 6
ER -