Institute for Pathobiochemistry, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Autophagy. 2011 Jul;7(7):795-8. doi: 10.4161/auto.7.7.15844.
There is a reciprocal change in the expression of two members of the BAG (Bcl-2-associated athanogen) family, BAG1 and BAG3, during cellular aging and under acute stress ("BAG1-BAG3-switch"). BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8. Also crucial for induction and execution of autophagy are sequestosome-1/p62 (SQSTM1/p62) and LC3, an autophagosome-associated protein. In this novel pathway, BAG3 mediates the targeting and transport of degradation-prone substrates into aggresomes via the microtubule-motor dynein. Interestingly, aggresome-targeting by BAG3 does not depend on substrate ubiquitination and is, therefore, involved in the clearance of misfolded proteins that are not ubiquitinated.
在细胞衰老和急性应激过程中，BAG（Bcl-2 相关抗凋亡基因）家族的两个成员 BAG1 和 BAG3 的表达呈相互变化（“BAG1-BAG3 转换”）。BAG3 最近被描述为一种新的巨自噬途径的介体，该途径利用热休克蛋白 70（HSP70）对错误折叠蛋白的特异性，还涉及其他蛋白伴侣，如 HSPB8。对于自噬的诱导和执行同样至关重要的还有自噬体相关蛋白 sequestosome-1/p62（SQSTM1/p62）和 LC3。在这个新途径中，BAG3 通过微管动力蛋白 dynein 将易于降解的底物靶向并转运到聚集体中。有趣的是，BAG3 对聚集体的靶向并不依赖于底物泛素化，因此参与了清除未被泛素化的错误折叠蛋白。
