Abstract
Abstract Proto-oncogenes ETV1, ETV4, and ETV5 belong to the PEA3 family of ETS transcription factors and have been identified recently in prostate cancer chromosomal rearrangements that result in their overexpression. Little is known, however, about their post-translational regulation. We previously showed that ETV1, ETV4, and ETV5 interact with the ubiquitin ligase COP1. COP1 together with its binding partner DET1 ubiquitinates ETV1, resulting in its proteasomal degradation. Importantly, truncation of ETV1 by the TMPRSS2:ETV1 translocation found in prostate cancer removes its COP1 binding motif and thereby enhances its stability. Consistent with a critical role for COP1 in regulating PEA3 transcription factors, COP1 deficiency in primary mouse prostate cells produced prostate intraepithelial neoplasia in vivo. The relationship between COP1 and ETV1 was also evident in human prostate cancer samples where loss of COP1 expression correlated with elevated ETV1 protein. I will discuss unpublished work that underscores the importance of COP1 as tumor suppressor.
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