The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs

被引：85

作者：

Signer, Robert A. J. ^{[1
,2
]}

Qi, Le ^{[1
]}

Zhao, Zhiyu ^{[1
]}

Thompson, David ^{[3
]}

Sigova, Alla A. ^{[4
]}

Fan, Zi Peng ^{[4
]}

DeMartino, George N. ^{[3
]}

Young, Richard A. ^{[4
,5
]}

Sonenberg, Nahum ^{[6
]}

Morrison, Sean J. ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Howard Hughes Med Inst, Dallas, TX 75390 USA

[2] Univ Calif San Diego, Moores Canc Ctr, Dept Med, Div Regenerat Med, La Jolla, CA 92093 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA

[4] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[5] MIT, Dept Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] McGill Univ, Goodman Canc Ctr, Dept Biochem, Montreal, PQ H3A 1A3, Canada

来源：

GENES & DEVELOPMENT | 2016年 / 30卷 / 15期

基金：

美国国家卫生研究院;

关键词：

4E-BP; protein synthesis; stem cell; TRANSLATIONAL CONTROL; SELF-RENEWAL; RIBOSOME BIOGENESIS; REPRESSOR; 4E-BP2; PROGENITOR CELLS; MICE LACKING; S6; KINASE; IN-VIVO; PHOSPHORYLATION; STRESS;

D O I：

10.1101/gad.282756.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Adult stem cells must limit their rate of protein synthesis, but the underlying mechanisms remain largely unexplored. Differences in protein synthesis among hematopoietic stem cells (HSCs) and progenitor cells did not correlate with differences in proteasome activity, total RNA content, mRNA content, or cell division rate. However, adult HSCs had more hypophosphorylated eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 as compared with most other hematopoietic progenitors. Deficiency for 4E-BP1 and 4E-BP2 significantly increased global protein synthesis in HSCs, but not in other hematopoietic progenitors, and impaired their reconstituting activity, identifying a mechanism that promotes HSC maintenance by attenuating protein synthesis.

引用

页码：1698 / 1703

页数：6

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