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

XBP-1S regulates the transcription of BiP by binding to the ERSE element located within the BiP promoter (2, 31) . We next wished to determine if the transcriptional activation of the BiP promoter by PCAF was mediated through ERSE as well. The wild-type and ERSE-mutant BiP-Luc reporter plasmids were utilized in the experiments. Extopic expression of PCAF significantly activated the Luc expression driven by the wild-type BiP promoter, while little or no effects were detected on the transcription driven by the ERSE-mutant BiP promoter ( Figure 5A) . Since the protein level of endogenous XBP-1S was low in the ER stress-free cells, only up to a 44% increase in BiP transcription was observed ( Figure 5A ). In the XBP-1Soverexpressing cells, PCAF exhibited stronger activation on the expression of luciferase driven by the wild-type BiP promoter ( Figure 5B, up to 3-fold) . However, no activating effects on the ERSE mutant BiP promoter were detected when both PCAF and XBP-1S were overexpressed ( Figure 5B ). Collectively, these results suggest that PCAF interacts with XBP-1S and mediates BiP transcription in an ERSE-dependent manner.