Sb. Klein et al., IDO MUTANTS CROSS RESISTANT TO TYPE-I INTERFERON RETAIN P91-DEPENDENTGENE INDUCTION, Journal of interferon research, 14(6), 1994, pp. 333-341
Genetic analyses of mutants have yielded valuable information about p9
1-associated interferon signal transduction. It was thus discovered th
at p91 is an essential protein for the induction of both type I and ty
pe II interferons, We previously reported the development of ME180 mut
ants resistant to interferon-gamma because of a signaling defect resul
ting in the loss of IDO induction, IDO does not respond to type I inte
rferon despite an ISRE-like sequence upstream of the coding region, Ho
wever, the IDO mutants were found to be cross-resistant to the growth-
inhibitory effects of type I interferon, We therefore examined the eff
ects of both types of interferon on interferon-stimulated gene mRNA ac
cumulation and examined alterations in cellular protein introduced by
the mutation, The induction of the p91-responsive gene 6-16 was not al
tered in either of the mutants, and the early-induced gene IRF1 exhibi
ted differences only in the kinetics of mRNA accumulation, The later i
nduced gene, p68, also exhibited different kinetics, possibly reflecti
ng the changes in IRF1, Immunoprecipitated p91 exhibited normal, inter
feron-induced phosphorylation in both mutants, Two-dimensional gel ele
ctrophoresis revealed that the mutant cells contained 20 peptides with
altered biochemistry, These results suggest that IDO induction is con
trolled by a distinct set of proteins not directly correlated with p91
activation,