PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription

Lew, Qiao Jing; Chu, Kai Ling; Lee, Jialing; Koh, Poh Ling; Rajasegaran, Vikneswari; Teo, Jin Yuan; Chao, Sheng-Hao

Functional significance of PCAF-XBP-1S interaction on the cellular target genes of XBP-1S, including BiP, CHOP and EDEM, was demonstrated in the PCAF overexpression and knockdown experiments (Figures 3-6 ). In addition, quantitative ChIP assays showed that XBP-1S recruited PCAF to the promoters of endogenous XBP-1S target genes in vivo, establishing direct functional connection between PCAF and XBP-1S ( Figure 7) . However, knockdown of PCAF by siRNA or shRNA did not completely inhibit the elevated transcription caused by XBP-1S (Figures 4 and 6 ). There are two possible explanations for these observations. First, both siRNA and shRNA against PCAF did not completely block the protein synthesis of PCAF ( Figures 4A and 6A ). Therefore, it is possible that the siRNA-and shRNA-transfected cells still have sufficient PCAF left to participate in the gene activation by XBP-1S. Secondly, PCAF may be one of the cellular co-factors responsible for XBP-1S-dependent transcription. Therefore, elimination of PCAF by RNA interference could only partially inhibit the transactivation of XBP-1S.