Lee Yu-Nee, Nechushtan Hovav, Figov Navah, Razin Ehud
Department of Biochemistry, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
Immunity. 2004 Feb;20(2):145-51. doi: 10.1016/s1074-7613(04)00020-2.
The involvement of microphthalmia transcription factor (MITF) in the function of mast cells, melanocytes, and osteoclasts has recently started to be investigated in depth. In a previous study, we found Hint to be associated with MITF in mast cells and showed that it suppresses MITF's transcriptional activity. Here, we have found that lysyl-tRNA synthetase (LysRS) is also associated with MITF and forms a multicomplex with MITF and Hint. We have also shown that Ap4A, an endogenous molecule consisting of two adenosine linked by four phosphate which is known to be synthesized by LysRS, is accumulated intracellularily above 700 microM in IgE-Ag-activated mast cells, binds to Hint, liberates MITF, and thus leads to the activation of MITF-dependent gene expression. This implies that LysRS plays a key role via Ap4A as an important signaling molecule in MITF transcriptional activity.
小眼畸形转录因子（MITF）在肥大细胞、黑素细胞和破骨细胞功能中的作用最近开始得到深入研究。在之前的一项研究中，我们发现Hint在肥大细胞中与MITF相关，并表明它抑制MITF的转录活性。在这里，我们发现赖氨酰-tRNA合成酶（LysRS）也与MITF相关，并与MITF和Hint形成多聚体复合物。我们还表明，Ap4A是一种由两个通过四个磷酸连接的腺苷组成的内源性分子，已知由LysRS合成，在IgE-Ag激活的肥大细胞中细胞内积累超过700微摩尔，与Hint结合，释放MITF，从而导致MITF依赖性基因表达的激活。这意味着LysRS通过Ap4A作为MITF转录活性中的重要信号分子发挥关键作用。
