| First Author | Piecyk M | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 15 | Pages | 4154-63 |
| PubMed ID | 10921895 | Mgi Jnum | J:88770 |
| Mgi Id | MGI:3037090 | Doi | 10.1093/emboj/19.15.4154 |
| Citation | Piecyk M, et al. (2000) TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha. EMBO J 19(15):4154-63 |
| abstractText | TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the 3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To determine the functional significance of this interaction, we used homologous recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce significantly more TNF-alpha protein than wild-type controls. The half-life of TNF-alpha transcripts is similar in wild-type and TIA-1(-/-) macrophages, indicating that TIA-1 does not regulate transcript stability. Rather, the absence of TIA-1 significantly increases the proportion of TNF-alpha transcripts that associate with polysomes, suggesting that TIA-1 normally functions as a translational silencer. TIA-1 does not appear to regulate the production of interleukin 1 beta, granulocyte-macrophage colony-stimulating factor or interferon gamma, indicating that its effects are, at least partially, transcript specific. Mice lacking TIA-1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress. |
