2018年8月16日 · RPAP2 reverses IRE1 phosphorylation, oligomerization, and RNase activation. This inhibits IRE1-mediated adaptive events, including activation of the cytoprotective transcription factor XBP1s, and ER-associated degradation of unfolded proteins. Furthermore, RIDD termination by RPAP2 unleashes DR5-mediated caspase activation and drives cell death.

2018年8月16日 · RPAP2 inhibits IRE1 activity in the face of unmitigated ER stress, aborting cytoporotective adaptation and promoting DR5-mediated apoptosis. Thus, coordination between the PERK and IRE1 branches of the UPR plays a critical role in determining cell fate in relation to ER-dependent proteostasis.

RPAP2 inhibits IRE1 activity in the face of unmitigated ER stress, aborting cytoporotective adaptation and promoting DR5-medi-ated apoptosis. Thus, coordination between the PERK and IRE1 branches of the UPR plays a critical role in determining cell …

研究团队发现细胞内存在一个与RNA聚合酶II（Pol II）紧密相互作用的蛋白——RPAP2，二者能够形成稳定的RPAP2-Pol II复合物，解析人源RPAP2-Pol II的高分辨结构，发现RPAP2蛋白结合在Pol II的jaw结构域附近，与转录起始前复合物的结构存在明显的空间位阻。

It has been proposed that the mechanism of IRE1 attenuation by PERK/RPAP2 aims to abort failed adaptation to ER stress and trigger apoptosis .

2022年4月26日 · RPAP2 prevents and disrupts Pol II-TFIIF interaction and impairs in vitro transcription initiation, suggesting a function in inhibiting PIC assembly. Loss of RPAP2 in cells leads to global accumulation of TFIIF and Pol II at promoters, indicating a critical role of RPAP2 in inhibiting PIC assembly independent of its putative phosphatase activity.

2024年11月5日 · This paper reveals that ER stress triggers apoptosis through cell-autonomous activation of DR5 and that during the adaptive phase of the UPR, IRE1 blocks PERK-driven DR5 mRNA upregulation via...

2024年4月1日 · Upon acute ER stress, PERK-prolonged activation leads to the phosphatase RPAP2 to interact and dephosphorylate IRE1, thereby decreasing its signaling (41). Another mechanism involving the protein tyrosine phosphatase PTP1B was shown to regulate both catalytic and scaffolding functions of IRE1 ( 105 , 121 ).

2025年2月15日 · Dampening pro-survival IRE1 signals by the phosphatase RPAP2 downstream of PERK during persistent ER stress switches the balance in favor of pro-apoptotic signaling by the PERK-CHOP axis,...

2025年2月8日 · Coordination between two branches of the unfolded protein response determines apoptotic cell fate so that PERK attenuates IRE1 via RPAP2 to abort failed endoplasmic reticulum stress adaptation and trigger apoptosis. These results suggest that RPAP2 controls Pol II activity through a direct interaction with Rpb6