Regulation of Pluripotency and Cellular Reprogramming by the Ubiquitin-Proteasome System

被引：292

作者：

Buckley, Shannon M. ^{[1
,2
,3
,4
]}

Aranda-Orgilles, Beatriz ^{[1
,2
,3
,4
]}

Strikoudis, Alexandros ^{[1
,2
,3
,4
]}

Apostolou, Effie ^{[7
]}

Loizou, Evangelia ^{[1
,2
,3
,4
]}

Moran-Crusio, Kelly ^{[1
,2
,3
,4
]}

Farnsworth, Charles L. ^{[9
]}

Koller, Antonius A. ^{[10
]}

Dasgupta, Ramanuj ^{[3
,4
]}

Silva, Jeffrey C. ^{[9
]}

Stadtfeld, Matthias ^{[5
,6
]}

Hochedlinger, Konrad ^{[7
,8
]}

Chen, Emily I. ^{[10
,11
]}

Aifantis, Iannis ^{[1
,2
,3
,4
]}

机构：

[1] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[3] NYU, Sch Med, Canc Inst, New York, NY 10016 USA

[4] NYU, Sch Med, Helen & Martin S Kimmel Stem Cell Ctr, New York, NY 10016 USA

[5] NYU, Sch Med, Dev Genet Program, Helen & Martin S Kimmel Stem Cell Ctr, New York, NY 10016 USA

[6] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA

[7] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[8] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[9] Cell Signaling Technol, Danvers, MA 01923 USA

[10] SUNY Stony Brook, Med Ctr, Prote Ctr, Stony Brook, NY 11794 USA

[11] SUNY Stony Brook, Med Ctr, Dept Pharmacol Sci, Stony Brook, NY 11794 USA

来源：

CELL STEM CELL | 2012年 / 11卷 / 06期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; SELF-RENEWAL; C-MYC; DIFFERENTIATION; DEGRADATION; MECHANISMS; EXPRESSION; ES; DEUBIQUITINATION; TRANSCRIPTION;

D O I：

10.1016/j.stem.2012.09.011

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Although transcriptional regulation of stem cell pluripotency and differentiation has been extensively studied, only a small number of studies have addressed the roles for posttranslational modifications in these processes. A key mechanism of posttranslational modification is ubiquitination by the ubiquitin-proteasome system (UPS). Here, using shotgun proteomics, we map the ubiquitinated protein landscape during embryonic stem cell (ESC) differentiation and induced pluripotency. Moreover, using UPS-targeted RNAi screens, we identify additional regulators of pluripotency and differentiation. We focus on two of these proteins, the deubiquitinating enzyme Psmd14 and the E3 ligase Fbxw7, and characterize their importance in ESC pluripotency and cellular reprogramming. This global characterization of the UPS as a key regulator of stem cell pluripotency opens the way for future studies that focus on specific UPS enzymes or ubiquitinated substrates.

引用

页码：783 / 798

页数：16

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