The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo.
Suppressor of Cytokine Signaling-1 (SOCS-1) is an essential physiological inhibitor of IFN-gamma signaling. Mice lacking this gene die in the early postnatal period from a disease characterized by hyperresponsiveness to endogenous IFN-gamma. The SOCS box is a C-terminal domain shared with over 30 other proteins that links SOCS proteins to an E3 ubiquitin ligase activity and the proteasome, but whether it contributes to inhibition of cytokine signaling is currently disputed. We have deleted only the SOCS box of the SOCS-1 gene in mice and show that such mice have an increased responsiveness to IFN-gamma and slowly develop a fatal inflammatory disease. These results demonstrate that deletion of the SOCS box leads to a partial loss of function of SOCS-1.
Zhang
J G
JG
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Parkville, Vic 3050, Australia.
Metcalf
D
D
Rakar
S
S
Asimakis
M
M
Greenhalgh
C J
CJ
Willson
T A
TA
Starr
R
R
Nicholson
S E
SE
Carter
W
W
Alexander
W S
WS
Hilton
D J
DJ
Nicola
N A
NA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D016207:Cytokines; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins