NCOA3 and Familial prostate cancer: While wild-type SPOP protein interacts directly with steroid receptor coactivator SRC-3 and enhances its ubiquitin-dependent proteasomal degradation to control the transcriptional activity of androgen receptor (AR), it has been recently demonstrated that most prostate cancer-associated SPOP mutants lack the capacity to promote the turnover of SRC-3 protein and thus display attenuated tumor suppressor effects in prostate cancer cell lines [15].