Breast cancer regulation by traffic and degradation of ErbB family

ERBB2/ErbB3异源二聚体在多种乳腺癌中均有表达，该二聚体产生的信号在乳腺癌的恶性表型中起重要作用。在目前的研究中，我分析了杂二聚体是如何被降解的。ErbB2相对稳定，ErbB3被蛋白酶体和溶酶体持续降解。NRG1β刺激可诱导蛋白酶体依赖性降解。在测试的几个E3中，我鉴定了Nrdp1和另外两个泛素化ErbB3的E3。此外，ErbB3的胞内部分需要100个氨基酸的复合才能降解，这表明ErbB3可能是泛素化的靶点。

ErbB2/ErbB3 heterodimer is expressed on many breast cancers, and the signals derived from the dimer plays significant roles on malignant phenotypes. In the present study, I analyzed how the heterodimer is degraded. Whereas ErbB2 was relatively stable, ErbB3 was continuously degraded by the proteasome and lysosomes. NRG1βstimulation induced proteasome-dependent degradation. Among several E3s tested, I identified Nrdp1 and two additional E3s that ubiquitinated ErbB3.Further, intracellular portion of ErbB3 comprizing of 100 aminoacids was required for the degradation, suggesting the possible ubiquitination target of ErbB3.