Das Santasabuj, Lin Jun-Hsiang, Papamatheakis Joseph, Sykulev Yuri, Tsichlis Philip N
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Biol Chem. 2002 Nov 22;277(47):45172-80. doi: 10.1074/jbc.M204117200. Epub 2002 Sep 4.
Earlier studies have shown that Tvl-1 gives rise to at least two differentially spliced mRNAs, one of which (Tvl-S) encodes a protein that lacks amino acids 91-112. DNA binding of RFX complexes assembled in the presence of Tvl-S is impaired. As a result, Tvl-S does not support the expression of Class II major histocompatibility complex (MHC) genes. Here, we show that the reason Tvl-S is inactive as a transcriptional regulator of Class II MHC genes is that the RFX complexes assembled in the presence of Tvl-S are unstable. Additionally, we show that interferon-gamma, which induces Class II MHC gene expression in 293 cells, promotes a shift in the splicing pattern of RFXANK/Tvl-1 toward the transcriptionally active Tvl-L isoform, suggesting that differential splicing of Tvl-1 is a signal-regulated process. Finally, we show that Tvl-1 regulates the expression of non-MHC genes. One such gene encodes the ephrin receptor EphA3. Since both Tvl-L and Tvl-S are identical in their ability to induce the expression of EphA3, we conclude that Tvl-1 regulates the expression of non-MHC genes by RFX-independent mechanisms.
早期研究表明，Tvl-1至少产生两种差异剪接的mRNA，其中一种（Tvl-S）编码一种缺少氨基酸91-112的蛋白质。在Tvl-S存在下组装的RFX复合物的DNA结合能力受损。因此，Tvl-S不支持II类主要组织相容性复合体（MHC）基因的表达。在此，我们表明Tvl-S作为II类MHC基因的转录调节因子无活性的原因是在Tvl-S存在下组装的RFX复合物不稳定。此外，我们表明在293细胞中诱导II类MHC基因表达的干扰素-γ促进RFXANK/Tvl-1的剪接模式向转录活性的Tvl-L异构体转变，这表明Tvl-1的差异剪接是一个信号调节过程。最后，我们表明Tvl-1调节非MHC基因的表达。其中一个这样的基因编码ephrin受体EphA3。由于Tvl-L和Tvl-S在诱导EphA3表达的能力上是相同的，我们得出结论，Tvl-1通过不依赖RFX的机制调节非MHC基因的表达。
