| First Author | Nikolcheva T | Year | 2002 |
| Journal | J Clin Invest | Volume | 110 |
| Issue | 1 | Pages | 119-26 |
| PubMed ID | 12093895 | Mgi Jnum | J:77476 |
| Mgi Id | MGI:2181848 | Doi | 10.1172/JCI15336 |
| Citation | Nikolcheva T, et al. (2002) A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes. J Clin Invest 110(1):119-26 |
| abstractText | Activation of T lymphocytes by specific antigen triggers a 3- to 7-day maturation process. Terminal differentiation begins late after T cell activation and involves expression of effector genes, including the chemokine RANTES and its major transcriptional regulator, RANTES factor of late-activated T lymphocytes-1 (RFLAT-1). In this article we demonstrate that RFLAT-1 expression is translationally regulated through its 5'-UTR and in a cell type-specific manner. Overexpression of the translation initiation factor eIF4E increases RFLAT-1 protein, while inhibition of Mnk1, which phosphorylates eIF4E, reduces RFLAT-1 production, indicating cap-dependent translational regulation. These events are regulated by ERK-1/2 and p38 MAP kinases and allow T cells to rapidly adjust RANTES expression in response to changes in the cellular environment, such as stress and/or growth factors. These findings provide a molecular mechanism for a rheostat effect of increasing or decreasing RANTES expression at sites of inflammation. Memory T cells, already poised to make RANTES, are finely regulated by translational control of the major transcription factor regulating RANTES expression. This is the first example of such a mechanism regulating a chemokine, but it seems likely that this will prove to be a general way for cells to rapidly respond to stress, cytokines, and other proinflammatory factors in their local environment. |
