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

Basal transcription of HTLV-1 occurs after proviral integration into the host cell genome and induces the initial expression of HTLV-1 proteins, including the transactivator, Tax, followed by Tax transactivation to boost the synthesis of viral transcripts. Two HATs, PCAF and p300, have been shown to interact with Tax and play a role in Tax-activated viral transcription (26, (33) (34) (35) . Tax, which does not bind to DNA by itself, activates HTLV-1 transcription through three 21-bp repeats known as TRE, located within the promoter of HTLV-1. Each 21-bp TRE repeat contains a CREB/ ATF binding site and is known to associate with CREB/ ATF family proteins (36, 37) . Tax binds to TREs through the interaction with CREB/ATF family proteins (including XBP-1S, CREB1 and CREB2) and recruits PCAF/p300 to HTLV-1 promoter, resulting in Tax transactivation (26, (33) (34) (35) . We previously found that XBP-1S bound to Tax and induced stronger Tax transactivation than other CREB/ATF family proteins (26) . Interestingly, XBP-1S also stimulated basal transcription of HTLV-1, while CREB1 and CREB2 did not show any activating effects, suggesting a crucial role for XBP-1S during the early phase of viral transcription as well (26) . No interaction between PCAF and CREB1 was detected in Co-IP analyses ( Figure 1A ). This observation could explain why CREB1 and other CREB/ATF family proteins fail to up-regulate HTLV-1 transcription in the absence of Tax. In contrast, the requirement for PCAF in the XBP-1S-dependent HTLV-1 basal transcription was clearly demonstrated in the cell-based reporter assays ( Figures 3A and 4A) .