Protor-2 interacts with tristetraprolin to regulate mRNA stability during stress.
Protor-2 interacts with tristetraprolin to regulate mRNA stability during stress.
复制标题
DOI：
10.1016/j.cellsig.2011.09.015
复制
发表时间：
2012-01
影响因子：
4.8
通讯作者：
Gera J
中科院分区：
文献类型：
--
作者：
Holmes B;Artinian N;Anderson L;Martin J;Masri J;Cloninger C;Bernath A;Bashir T;Benavides-Serrato A;Gera J
The A/U-rich RNA binding protein tristetraprolin (TTP) is an mRNA destabilizing factor which plays a role in the regulated turnover of many transcripts encoding proteins involved in immune function and cell growth control. TTP also plays a role in stress-induced destabilization of mRNAs. Here we report the interaction of TTP with a component of the mTORC2 kinase, Protor-2 (PRR5-L, protein Q6MZQ0/FLJ14213/CAE45978). Protor-2 is structurally similar to human PRR5 and has been demonstrated to bind mTORC2 via Rictor and/or Sin1 and may signal downstream events promoting apoptosis. Protor-2 dissociates from mTORC2 upon hyperactivation of the kinase and is not required for mTORC2 integrity or activity. We identified Protor-2 in a yeast two-hybrid screen as a TTP interactor using the C-terminal mRNA decay domain of TTP as bait. The interaction of Protor-2 with TTP was also confirmed in vivo in co-immunoprecipitation experiments and Protor-2 was also detected in immunoprecipitates of rictor. Protor-2 was shown to stimulate TTP-mediated mRNA turnover of several TTP-associated mRNAs (TNF-α, GM-CSF, IL-3 and COX-2) in Jurkat cells when overexpressed while the half-lives of transcripts which do not decay via a TTP-mediated mechanism were unaffected. Knockdown of Protor-2 via RNAi inhibited TTP-mediated mRNA turnover of these TTP-associated mRNAs and inhibited association of TTP with cytoplasmic stress granules (SG) or mRNA processing bodies (P-bodies) following induction of the integrated stress response. These results suggest that Protor-2 associates with TTP to accelerate TTP-mediated mRNA turnover and functionally links the control of TTP regulated mRNA stability to mTORC2 activity.
登录
查看更多内容
DOI：
10.1073/pnas.95.11.6245
发表时间：
1998-05-26
影响因子：
11.1
作者：
Ludin, K;Jiang, R;Carlson, M
通讯作者：
Carlson, M
DOI：
10.1126/science.1199498
发表时间：
2011-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hsu PP;Kang SA;Rameseder J;Zhang Y;Ottina KA;Lim D;Peterson TR;Choi Y;Gray NS;Yaffe MB;Marto JA;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
4.9
作者：
Carrick DM;Lai WS;Blackshear PJ
通讯作者：
Blackshear PJ
影响因子：
3.3
作者：
Albig, AR;Decker, CJ
通讯作者：
Decker, CJ
影响因子：
11.2
作者：
McDonald, Paul C.;Oloumi, Arusha;Dedhar, Shoukat
通讯作者：
Dedhar, Shoukat