Global Identification of Modular Cullin-RING Ligase Substrates

被引：379

作者：

Emanuele, Michael J. ^{[1
,2
,6
]}

Elia, Andrew E. H. ^{[1
,2
,3
,6
]}

Xu, Qikai ^{[1
,2
,6
]}

Thoma, Claudio R. ^{[1
,2
,6
]}

Izhar, Lior ^{[1
,2
,6
]}

Leng, Yumei ^{[1
,2
,6
]}

Guo, Ailan ^{[4
]}

Chen, Yi-Ning ^{[5
]}

Rush, John ^{[4
]}

Hsu, Paul Wei-Che ^{[5
]}

Yen, Hsueh-Chi Sherry ^{[1
,2
,5
,6
]}

Elledge, Stephen J. ^{[1
,2
,6
]}

机构：

[1] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

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

[5] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan

[6] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

CELL | 2011年 / 147卷 / 02期

关键词：

CUL3-BASED E3 LIGASE; UBIQUITIN-LIGASE; PROTEIN; SCF; INHIBITOR; NUSAP; DEGRADATION; ACTIVATION; EXPRESSION; CATALYZES;

D O I：

10.1016/j.cell.2011.09.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cullin-RING ligases (CRLs) represent the largest E3 ubiquitin ligase family in eukaryotes, and the identification of their substrates is critical to understanding regulation of the proteome. Using genetic and pharmacologic Cullin inactivation coupled with genetic (GPS) and proteomic (QUAINT) assays, we have identified hundreds of proteins whose stabilities or ubiquitylation status are regulated by CRLs. Together, these approaches yielded many known CRL substrates as well as a multitude of previously unknown putative substrates. We demonstrate that one substrate, NUSAP1, is an SCFCyclin F substrate during S and G2 phases of the cell cycle and is also degraded in response to DNA damage. This collection of regulated substrates is highly enriched for nodes in protein interaction networks, representing critical connections between regulatory pathways. This demonstrates the broad role of CRL ubiquitylation in all aspects of cellular biology and provides a set of proteins likely to be key indicators of cellular physiology.

引用

页码：459 / 474

页数：16

共 49 条

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CRL4Cdt2 Master coordinator of cell cycle progression and genome stability [J].