TRIM8/GERP RING finger protein interacts with SOCS-1.
Members of the suppressor of cytokine signaling (SOCS) family of signaling molecules regulate the activation of cytokine signaling. Experimental evidence indicates that SOCS expression is induced by cytokines and pro-inflammatory stimuli and is controlled at both the transcriptional and post-transcriptional levels. SOCS proteins are unstable and seem to be rapidly degraded by proteasomal pathways. However, the mechanisms by which SOCS protein levels are regulated remain unclear. Here, we show that TRIM8/GERP, a RING finger protein, interacts with SOCS-1 in vitro and in vivo. TRIM8/GERP, previously identified as a new member of the family of proteins containing a tripartite motif (TRIM), is a 551-amino acid RING finger protein conserved across species. TRIM8/GERP expression can be induced by interferon-gamma in epithelial and lymphoid cells. Coexpression of TRIM8/GERP with SOCS-1 decreases SOCS-1 protein stability and levels. Functionally, expression of TRIM8/GERP decreases the repression of interferon-gamma signaling mediated by SOCS-1. These data suggest that TRIM8/GERP may be a regulator of SOCS-1 function.
Toniato
Elena
E
Department of Medicine and Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Chen
X Peter
XP
Losman
Julie
J
Flati
Vincenzo
V
Donahue
Liz
L
Rothman
Paul
P
D000595:Amino Acid Sequence; D000906:Antibodies; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014162:Transfection; D016335:Zinc Fingers
D000906:Antibodies; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C418604:TRIM8 protein, human