The bromodomain and extraterminal (BET) family of proteins comprises four members—
BRD2, BRD3, BRD4 and the testis-specific isoform BRDT—that largely function as
transcriptional coactivators,, and play critical roles in various cellular processes, including
the cell cycle, apoptosis, migration and invasion,. BET proteins enhance the oncogenic
functions of major cancer drivers by elevating the expression of these drivers, such as c-Myc
in leukemia,, or by promoting the transcriptional activities of oncogenic factors, such as AR …

Editorial Comment: The results of this study uncover a critical tumor suppressive role of
SPOP in prostate cancer whereby it earmarks the BRD4 oncoprotein for timely destruction.
Furthermore, the authors show that impairment of this signaling axis by mutations at the level
of either the E3 ligase (SPOP) or the substrate (BRD4) can prevent SPOP mediated
destruction of BRD4 by disrupting SPOP-BRD4 interaction, leading to stabilization and
cooperation of BRD4 with various oncogenic transcription factors, including androgen …