The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications

Youzhou Sang, Fan Yan and Xiubao Ren _

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Oncotarget. 2015; 6:42590-42602. https://doi.org/10.18632/oncotarget.6052

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Youzhou Sang1,3,4, Fan Yan1,3,4 and Xiubao Ren2,3,4

1 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

2 Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

3 National Clinical Research Center of Cancer, Tianjin, China

4 Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China

Correspondence to:

Xiubao Ren, email:

Keywords: CRL4, CUL4, ubiquitination, cancer

Received: April 08, 2015 Accepted: September 23, 2015 Published: October 09, 2015


CRLs (Cullin-RING E3 ubiquitin ligases) are the largest E3 ligase family in eukaryotes, which ubiquitinate a wide range of substrates involved in cell cycle regulation, signal transduction, transcriptional regulation, DNA damage response, genomic integrity, tumor suppression and embryonic development. CRL4 E3 ubiquitin ligase, as one member of CRLs family, consists of a RING finger domain protein, cullin4 (CUL4) scaffold protein and DDB1–CUL4 associated substrate receptors. The CUL4 subfamily includes two members, CUL4A and CUL4B, which share extensively sequence identity and functional redundancy. Aberrant expression of CUL4 has been found in a majority of tumors. Given the significance of CUL4 in cancer, understanding its detailed aspects of pathogenesis of human malignancy would have significant value for the treatment of cancer. Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor. Finally, we discuss its potential value in cancer therapy.

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