Interaction between two glaucoma genes, optineurin and myocilin
Interaction between two glaucoma genes, optineurin and myocilin
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DOI：
10.1111/j.1365-2443.2007.01102.x
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发表时间：
2007-08-01
期刊：
影响因子：
2.1
通讯作者：
Yue, Beatrice Y. J. T.
中科院分区：
文献类型：
--
作者：
Park, Bum-Chan;Tibudan, Martin;Yue, Beatrice Y. J. T.
Myocilin（MYOC）和optineurin（OPTN）是与青光眼（一种主要致盲疾病）相关的两个基因。为了研究MYOC和OPTN基因之间可能的分子相互作用，我们过表达MYOC并检查其对人小梁网（TM）细胞中内源性OPTN水平的影响，反之亦然。我们注意到过表达MYOC不影响OPTN水平，而OPTN过表达诱导内源性MYOC的上调。在其他眼和非眼细胞类型（包括PC12细胞）中也观察到这种诱导。此外，发现当用神经生长因子（NGF）处理的PC12细胞经历分化时，OPTN和MYOC基因的内源性水平增加。OPTN的过表达导致MYOC mRNA的周转率延长，但对MYOC基因的启动子活性影响不大。过表达的OPTN定位于细胞质中，而不是易位到细胞核中。这些结果表明OPTN和MYOC基因之间存在相互作用。OPTN对MYOC表达的调节主要通过控制mRNA稳定性来实现。
Myocilin (MYOC) and optineurin (OPTN) are two genes linked to glaucoma, a major blinding disease. To investigate the possible molecular interactions between MYOC and OPTN genes, we over-expressed MYOC and examined its effect on the level of endogenous OPTN in human trabecular meshwork (TM) cells and vice versa. We noted that over-expressing MYOC did not affect the OPTN level, whereas OPTN over-expression induced an up-regulation of the endogenous MYOC. This induction was also observed in other ocular and non-ocular cell types including PC12 cells. The endogenous levels of both OPTN and MYOC genes were in addition found increased when PC12 cells underwent differentiation upon treatment with nerve growth factor (NGF). Over-expression of OPTN resulted in prolonged turnover rate of MYOC mRNA but had little effect on the promoter activity of the MYOC gene. The over-expressed OPTN was localized in the cytoplasm, not translocated into the nucleus. These results indicate that interaction exists between OPTN and MYOC genes. Regulation of MYOC expression by OPTN is achieved primarily through control of the mRNA stability.