The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation
The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation
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DOI：
10.1073/pnas.96.5.2071
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Baca, M
中科院分区：
文献类型：
--
作者：
Zhang, JG;Farley, A;Baca, M
细胞因子信号转导抑制因子（suppressors of cytokine signaling，SOCS）家族蛋白是细胞内多种细胞因子信号转导途径的抑制因子。它们的表达由Janus激酶/信号转导子和转录激活子的细胞因子激活诱导（JAK/STAT）途径，并且它们通过随后通过与活化的JAK或与受体直接相互作用来抑制JAK/STAT途径而充当负反馈环，这些相互作用至少部分由SOCS蛋白的SH 2结构域介导，但这些蛋白也含有高度保守的C-末端同源结构域称为SOCS盒。在这里，我们表明，SOCS盒介导的相互作用与延伸蛋白B和C，这反过来又可能耦合SOCS蛋白和它们的底物的蛋白酶体蛋白降解途径。与含F盒蛋白家族类似，SOCS蛋白似乎可以作为衔接分子，将活化的细胞信号蛋白靶向蛋白降解途径。
The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors, These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.