Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex -Involvement in estrogen receptor alpha signaling pathway

We have reported previously the physical interaction of B-cell translocatio n gene proteins (BTG)1 and BTG2 with the mouse protein CAF1 (CCR4-associate d factor 1) and suggested that these proteins may participate, through thei r association with CAF1, in transcription regulation. Here we describe the in vitro and in vivo association of these proteins with hPOP2, the human pa ralog of hCAF1, The physical and functional relationships between the BTG p roteins and their partners hCAF1 and hPOP2 were investigated to find out ho w these interactions affect cellular processes, and in particular transcrip tion regulation. We defined their interaction regions and examined their ex pression in various human tissues. We also show functional data indicating their involvement in estrogen receptor a (ER alpha)-mediated transcription regulation. We found that BTG1 and BTG2, probably through their interaction with CAF1 via a CCR4-like complex, can play both positive or negative role s in regulating the ER alpha function. In addition, our results indicate th at two LXXLL motifs, referred to as nuclear receptor boxes, present in both BTG1 and BTG2, are involved in the regulation of ER alpha -mediated activa tion.