| First Author | Gregorieff A | Year | 2000 |
| Journal | J Biol Chem | Volume | 275 |
| Issue | 28 | Pages | 21596-604 |
| PubMed ID | 10764816 | Mgi Jnum | J:63471 |
| Mgi Id | MGI:1861044 | Doi | 10.1074/jbc.M910087199 |
| Citation | Gregorieff A, et al. (2000) Regulation of SOCS-1 expression by translational repression. J Biol Chem 275(28):21596-604 |
| abstractText | Accumulating evidence demonstrates that cytokine receptor signaling is negatively regulated by a family of Src homology 2 domain-containing adaptor molecules termed SOCS (suppressor of cytokine signaling). Previous studies have indicated that the expression of SOCS-related molecules is tightly controlled at the level of transcription. Furthermore, it has been reported that SOCS polypeptides are relatively unstable in cells, unless they are associated with elongins B and C. Herein, we document the existence of a third mechanism of regulation of SOCS function. Our data showed that expression of SOCS-1, a member of the SOCS family, is strongly repressed at the level of translation initiation. Structure-function analyses indicated that this effect is mediated by the 5' untranslated region of socs-1 and that it relates to the presence of two upstream AUGs in this region. Further studies revealed that socs-1 translation is cap-dependent and that it is modulated by eIF4E-binding proteins. In combination, these results uncover a novel level of regulation of SOCS-related molecules. Moreover, coupled with previous findings, they suggest that SOCS expression is tightly regulated through multiple mechanisms, in order to avoid inappropriate interference with cytokine-mediated effects. |
