Lu Qun, Hong Wang
Guangdong College of Pharmacy, Guangzhou, Guangdong, China.
Cell Signal. 2009 Jul;21(7):1054-9. doi: 10.1016/j.cellsig.2009.02.020. Epub 2009 Mar 1.
Matrix metalloproteinases (MMPs) are a major group of enzymes that regulate cell matrix composition. In this paper, our results show that c-Myc significantly induced vascular smooth muscle cells (VSMCs) migration and invasion, compared with the results, the T58A had more effectively than WT c-Myc, which was associated with c-Myc increased MMP-2 gene expression and activity. Silenced c-Myc led to reduce MMP-2 gene expression and activity, as well as decrease VSMC migration and invasion, indicating c-Myc is required for MMP-2 mediated VSMC migration and invasion. However, S62A had no effect on VSMC migration and invasion, which was in line with S62A had no effect on the c-Myc transcriptional activity. To better understand whether Bcl2 cooperate with c-Myc on MMP-2 function, our data show that although Bcl2 had no effect on the MMP-2 activity, the coexpressing c-Myc and Bcl2 significantly increased MMP-2 gene expression and activity. Our results suggest that phosphorylation of Bcl2 (T70E and EEE) had more effectively on the MMP-2 activity, which resulted from T70E and EEE severely increased c-Myc transcriptional activity by directly binding to c-Myc. The findings show that phosphorylation of Bcl2 enhanced c-Myc-mediated MMP-2 activity.
基质金属蛋白酶（MMPs）是调节细胞外基质组成的主要酶类。在本文中，我们的结果表明，与野生型c-Myc相比，c-Myc显著诱导血管平滑肌细胞（VSMCs）迁移和侵袭，而T58A比野生型c-Myc更有效，这与c-Myc增加MMP-2基因表达和活性有关。沉默c-Myc导致MMP-2基因表达和活性降低，以及VSMC迁移和侵袭减少，表明c-Myc是MMP-2介导的VSMC迁移和侵袭所必需的。然而，S62A对VSMC迁移和侵袭没有影响，这与S62A对c-Myc转录活性没有影响一致。为了更好地理解Bcl2是否与c-Myc在MMP-2功能上协同作用，我们的数据表明，虽然Bcl2对MMP-2活性没有影响，但共表达c-Myc和Bcl2显著增加MMP-2基因表达和活性。我们的结果表明，Bcl2（T70E和EEE）的磷酸化对MMP-2活性更有效，这是因为T70E和EEE通过直接结合c-Myc严重增加了c-Myc转录活性。这些发现表明，Bcl2的磷酸化增强了c-Myc介导的MMP-2活性。
