Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation.
Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation.
复制标题
DOI：
10.1016/j.devcel.2013.11.013
复制
发表时间：
2013-12-23
影响因子：
11.8
通讯作者：
Goldfarb, Adam N.
中科院分区：
文献类型：
--
作者：
Elagib, Kamaleldin E.;Rubinstein, Jeremy D.;Delehanty, Lorrie L.;Ngoh, Valerie S.;Greer, Peter A.;Li, Shuran;Lee, Jae K.;Li, Zhe;Orkin, Stuart H.;Mihaylov, Ivailo S.;Goldfarb, Adam N.
Megakaryocyte morphogenesis employs a “hypertrophy-like” developmental program, dependent on P-TEFb kinase activation and cytoskeletal remodeling. P-TEFb activation classically occurs by a feedback regulated process of signal-induced, reversible release of active Cdk9-cyclin T modules from large inactive 7SK snRNP complexes. Here we have identified an alternative pathway of irreversible P-TEFb activation in megakaryopoiesis, mediated by dissolution of the 7SK snRNP complex. In this pathway calpain 2 cleavage of the core 7SK snRNP component MePCE promoted P-TEFb release and consequent upregulation of a cohort of cytoskeleton remodeling factors, including α-actinin-1. In a subset of human megakaryocytic leukemias, the transcription factor GATA1 undergoes truncating mutation (GATA1s). Here we linked the GATA1s mutation to defects in megakaryocytic upregulation of calpain 2 and of P-TEFb-dependent cytoskeletal remodeling factors. Restoring calpain 2 expression in GATA1s-mutant megakaryocytes rescued normal development, implicating this morphogenetic pathway as a target in human leukemogenesis.
登录
查看更多内容
影响因子：
3.7
作者：
Krueger BJ;Varzavand K;Cooper JJ;Price DH
通讯作者：
Price DH
影响因子：
9.8
作者：
Kadri Z;Shimizu R;Ohneda O;Maouche-Chretien L;Gisselbrecht S;Yamamoto M;Romeo PH;Leboulch P;Chretien S
通讯作者：
Chretien S
影响因子：
20.3
作者：
Gilles, Laure;Bluteau, Dominique;Raslova, Hana
通讯作者：
Raslova, Hana
DOI：
10.1073/pnas.0511150103
发表时间：
2006-02-28
影响因子：
11.1
作者：
Bourquin, JP;Subramanian, A;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
7.7
作者：
Li Y;Ma J;Zhu H;Singh M;Hill D;Greer PA;Arnold JM;Abel ED;Peng T
通讯作者：
Peng T