A novel docking site on Mediator is critical for activation by VP16 in mammalian cells.
ARC92/ACID1 was identified as a novel specific target of the herpes simplex transactivator VP16 using an affinity purification procedure. Characterization of the protein revealed tight interactions with human Mediator mediated through a von Willebrand type A domain. ARC92/ACID1 further contains a novel activator-interacting domain (ACID), which it shares with at least one other human gene termed PTOV1/ACID2. The structure of ARC92/ACID1 is of ancient origin but is conserved in mammals and in selected higher eukaryotes. A subpopulation of Mediator is associated with ARC92/ACID1, which is specifically required for VP16 activation both in vitro and in mammalian cells, but is dispensable for other activators such as SP1. Despite many known targets of VP16, ARC92/ACID1 appears to impose a critical control on transcription activation by VP16 in mammalian cells.
Mittler
Gerhard
G
National Research Center for Environment and Health-GSF, Institute of Molecular Immunology, Gene Expression, Marchionini-Strasse 25, D-81377 Munich, Germany.
Stühler
Thomas
T
Santolin
Lisa
L
Uhlmann
Thomas
T
Kremmer
Elisabeth
E
Lottspeich
F
F
Berti
Lucia
L
Meisterernst
Michael
M
D000818:Animals; D002460:Cell Line; D003360:Cosmids / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005822:Genetic Vectors; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D018076:DNA, Complementary; D017405:Herpes Simplex Virus Protein Vmw65; D011994:Recombinant Proteins