Aberrant estrogen receptor-α (ERα) signaling is recognized as a major contributor to the development of breast cancer. However， the molecular mechanism underlying the regulation of ERα in breast cancer is still inconclusive. In this study， we showed that the transcription factor 21 (TCF21) interacted with ERα， and repressed its transcriptional activity in a HDACs-dependent manner. We also showed that TCF21 could be sumoylated by the small ubiquitin-like modifier SUMO1， and this modification could be reversed by SENP1. Sumoylation of TCF21 occurred at lysine residue 24 (K24). Substitution of K24 with arginine resulted in complete abolishment of sumoylation. Sumoylation stabilized TCF21， but did not... More
Aberrant estrogen receptor-α (ERα) signaling is recognized as a major contributor to the development of breast cancer. However， the molecular mechanism underlying the regulation of ERα in breast cancer is still inconclusive. In this study， we showed that the transcription factor 21 (TCF21) interacted with ERα， and repressed its transcriptional activity in a HDACs-dependent manner. We also showed that TCF21 could be sumoylated by the small ubiquitin-like modifier SUMO1， and this modification could be reversed by SENP1. Sumoylation of TCF21 occurred at lysine residue 24 (K24). Substitution of K24 with arginine resulted in complete abolishment of sumoylation. Sumoylation stabilized TCF21， but did not affect its subcellular localization. Sumoylation of TCF21 also enhanced its interaction with HDAC1/2 without affecting its interaction with ERα. Moreover， sumoylation of TCF21 promoted its repression of ERα transcriptional activity， and increased the recruitment of HDAC1/2 to the pS2 promoter. Consistent with these observations， sumoylation of TCF21 could inhibit the growth of ERα-positive breast cancer cells and decreased the proportion of S-phase cells in the cell cycle. These findings suggested that TCF21 might act as a negative regulator of ERα， and its sumoylation inhibited the transcriptional activity of ERα through promoting the recruitment of HDAC1/2.
