Baert J-L, Beaudoin C, Monte D, Degerny C, Mauen S, de Launoit Y
UMR 8161, Institut de Biologie de Lille, CNRS/Université de Lille 1/Université de Lille 2/Institut Pasteur de Lille, IFR 142, Lille Cedex, France.
Oncogene. 2007 Jan 18;26(3):415-24. doi: 10.1038/sj.onc.1209801. Epub 2006 Jul 10.
ERM is a member of the ETS transcription factor family. High levels of the corresponding mRNA are detected in a variety of human breast cancer cell lines, as well as in aggressive human breast tumors. As ERM protein is almost undetectable in these cells, high degradation of this transcription factor has been postulated. Here we have investigated whether ERM degradation might depend on the proteasome pathway. We show that endogenous and ectopically expressed ERM protein is short-lived protein and undergoes proteasome-dependent degradation. Deletion mutagenesis studies indicate that the 61 C-terminal amino acids of ERM are critical for its proteolysis and serve as a degradation signal. Although ERM conjugates with ubiquitin, this post-translational modification does not depend on the C-terminal domain. We have used an Ets-responsive ICAM-1 reporter plasmid to show that the ubiquitin-proteasome pathway can affect transcriptional function of ERM. Thus, ERM is subject to degradation via the 26S proteasome pathway, and this pathway probably plays an important role in regulating ERM transcriptional activity.
ERM是ETS转录因子家族的成员。在多种人乳腺癌细胞系以及侵袭性人乳腺肿瘤中均检测到相应mRNA的高水平表达。由于在这些细胞中几乎检测不到ERM蛋白，因此推测该转录因子存在高度降解的情况。在此，我们研究了ERM的降解是否可能依赖于蛋白酶体途径。我们发现内源性和异位表达的ERM蛋白都是短寿命蛋白，并经历蛋白酶体依赖性降解。缺失诱变研究表明，ERM的61个C末端氨基酸对其蛋白水解至关重要，并作为降解信号。尽管ERM与泛素结合，但这种翻译后修饰并不依赖于C末端结构域。我们使用了一个Ets反应性ICAM-1报告质粒来表明泛素-蛋白酶体途径可以影响ERM的转录功能。因此，ERM通过26S蛋白酶体途径进行降解，并且该途径可能在调节ERM转录活性中起重要作用。
