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

Under the ER stress-free condition, our data clearly indicated that PCAF was required for XBP-1S-mediated transcriptional regulation (Figures 3-7) . However, results from QRT-PCR and quantitative ChIP showed that PCAF only exhibited limited involvement in the expression of XBP-1S target genes when UPR was induced ( Figure 8) . A recent study identified the regulatory subunit of phosphoinositide 3-kinase (PI3K) as a novel XBP-1S binding protein and demonstrated that the association between XBP-1S and the PI3K subunit could be UPR-dependent (32) . We examined the XBP-1S-PCAF protein-protein interaction under the normal or Tm-stressed conditions. As shown in Figure 9 , the interaction between XBP-1S and PCAF was not disrupted during UPR. On-going research focuses on the identification of the XBP-1S co-factor(s) required for the transactivation caused by XBP-1S once UPR is induced. GCN5, a HAT which shares 73% identity in amino acid sequence with PCAF (42), is a possible candidate for XBP-1S binding partner. The involvement of GCN5 in XBP-1S-dependent transcription and during UPR is currently under investigation.