Atlas on substrate recognition subunits of CRL2 E3 ligases

Siwei Wang, Wenjia Xia, Mantang Qiu, Xin Wang, Feng Jiang, Rong Yin and Lin Xu _

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Oncotarget. 2016; 7:46707-46716. https://doi.org/10.18632/oncotarget.8732

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Siwei Wang1,2,*, Wenjia Xia1,2,*, Mantang Qiu1,2, Xin Wang1,2, Feng Jiang1, Rong Yin1 and Lin Xu1

1 Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China

2 The Fourth Clinical College of Nanjing Medical University, Nanjing, China

* These authors have contributed equally to this work

Correspondence to:

Lin Xu, email:

Rong Yin, email:

Keywords: cullin-ring ligase(CRL); cullin2; E3 ligase; substrate recognition subunit (SRS)

Received: December 23, 2015 Accepted: April 02, 2016 Published: April 14, 2016


The Cullin2-type ubiquitin ligases belong to the Cullin-Ring Ligase (CRL) family, which is a crucial determinant of proteasome-based degradation processes in eukaryotes. Because of the finding of von Hippel-Lindau tumor suppressor (VHL), the Cullin2-type ubiquitin ligases gain focusing in the research of many diseases, especially in tumors. These multisubunit enzymes are composed of the Ring finger protein, the Cullin2 scaffold protein, the Elongin B&C linker protein and the variant substrate recognition subunits (SRSs), among which the Cullin2 scaffold protein is the determining factor of the enzyme mechanism. Substrate recognition of Cullin2-type ubiquitin ligases depends on SRSs and results in the degradation of diseases associated substrates by intracellular signaling events. This review focuses on the diversity and the multifunctionality of SRSs in the Cullin2-type ubiquitin ligases, including VHL, LRR-1, FEM1b, PRAME and ZYG11. Recently, as more SRSs are being discovered and more aspects of substrate recognition have been illuminated, insight into the relationship between Cul2-dependent SRSs and substrates provides a new area for cancer research.

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