Details

Autor(en) / Beteiligte

• Emanuele, Michael J.
• Elia, Andrew E.H.
• Xu, Qikai
• Thoma, Claudio R.
• Izhar, Lior
• Leng, Yumei
• Guo, Ailan
• Chen, Yi-Ning
• Rush, John
• Hsu, Paul Wei-Che
• Yen, Hsueh-Chi Sherry
• Elledge, Stephen J.

Titel

Global Identification of Modular Cullin-RING Ligase Substrates

Ist Teil von

• Cell, 2011-10, Vol.147 (2), p.459-474

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] ► Cullin-RING ligase (CRL) substrates were found in a fluorescence-based genetic screen ► A proteomic screen using ubiquitylation site enrichment found overlapping substrates ► CRL substrates are enriched as highly connected nodes within interaction networks ► NUSAP1 is targeted by SCFCyclin F during S and G2 and is degraded by UV DNA damage A combination of genetic and proteomic screens reveals cullin-RING ligase substrates and places these factors at key regulatory nodes in cellular networks.