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

Recent studies show that cellular UPR can be induced by infection of various viruses, including Kaposi's sarcoma-associated herpesvirus (13) , West Nile virus (14) , Japanese encephalitis virus (JEV) (15) , hepatitis C virus (16, 17) , human cytomegalovirus (HCMV) (18, 19) , dengue virus serotype 2 (DEN-2) (20) , severe acute respiratory syndrome coronavirus (21) , coronavirus (22) , Epstein-Barr virus (23) and Semliki Forest virus (24) . Some viruses, such as JEV and DEN-2, use the ER of host cells as the primary site of glycoprotein synthesis, genomic RNA replication and virus particle maturation, and thus trigger ER stress as well as UPR (15, 20) . In the other case, some viral proteins, such as HCMV US11, traffic to the ER of host cells and induce UPR (18) . The transactivator of human T-lymphotropic virus type 1 (HTLV-1), Tax, has been shown to be localized in the organelles associated with protein secretion including ER and Golgi complex (25) , raising the possibility that HTLV-1 may affect cellular UPR as well. We previously discovered that XBP-1S stimulates basal and Tax-activated transcription of HTLV-1. Infection of HTLV-1 was found to induce UPR and up-regulation the expression of several UPR genes, including XBP-1. Furthermore, XBP-1 was identified as one of the Tax target genes in cells (26) . Our results not only revealed a positive feedback loop between HTLV-1 and the host cells, but also suggested an important role for XBP-1 in transcriptional regulation of HTLV-1.