Breast cancer regulation by traffic and degradation of ErbB family

2011 Fiscal Year Final Research Report

• Project/Area Number: 22791265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Miyagi Cancer Center Research Institute
• Principal Investigator: SAKURAI Yu 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 共同研究員 (80451574)
• Project Period (FY): 2010 – 2011
• Keywords: 乳腺外科 / がん

Research Abstract

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.