Girard Martine, McPherson Peter S
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
FEBS Lett. 2008 Mar 19;582(6):961-6. doi: 10.1016/j.febslet.2008.02.042. Epub 2008 Feb 26.
We recently identified receptor-mediated endocytosis 8 (RME-8), a DnaJ domain protein localized to endosomes. We now demonstrate that RME-8 depletion leads to decreased levels of epidermal growth factor receptor (EGFR) without influencing receptors that primarily recycle to the plasma membrane. Decreases in EGFR are detected at both surface and intracellular pools and result from increased rates of EGFR degradation. Interestingly, RME-8 depletion also decreases EGFR levels in breast cancer cell lines in which overexpression of the EGFR family member ErbB2 has been shown to protect EGFR from degradation. These data implicate RME-8 in sorting decisions influencing EGFR at the level of endosomes and point to RME-8 as a potential regulatory target in ErbB2-positive breast cancers.
我们最近鉴定出受体介导的内吞作用8（RME-8），一种定位于内体的DnaJ结构域蛋白。我们现在证明，RME-8的缺失导致表皮生长因子受体（EGFR）水平降低，而不影响主要循环至质膜的受体。在表面和细胞内池均检测到EGFR的减少，这是由于EGFR降解速率增加所致。有趣的是，RME-8的缺失也降低了乳腺癌细胞系中EGFR的水平，在这些细胞系中，EGFR家族成员ErbB2的过表达已被证明可保护EGFR不被降解。这些数据表明RME-8在内体水平影响EGFR的分选决策中起作用，并指出RME-8是ErbB2阳性乳腺癌的潜在调控靶点。
