Title | The emerging role for Cullin 4 family of E3 ligases in tumorigenesis. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Cheng J, Guo J, North BJ, Tao K, Zhou P, Wei W |
Journal | Biochim Biophys Acta Rev Cancer |
Volume | 1871 |
Issue | 1 |
Pagination | 138-159 |
Date Published | 2019 01 |
ISSN | 1879-2561 |
Keywords | Animals, Carcinogenesis, Humans, Mice, Neoplasms, Ubiquitin-Protein Ligases |
Abstract | As a member of the Cullin-RING ligase family, Cullin-RING ligase 4 (CRL4) has drawn much attention due to its broad regulatory roles under physiological and pathological conditions, especially in neoplastic events. Based on evidence from knockout and transgenic mouse models, human clinical data, and biochemical interactions, we summarize the distinct roles of the CRL4 E3 ligase complexes in tumorigenesis, which appears to be tissue- and context-dependent. Notably, targeting CRL4 has recently emerged as a noval anti-cancer strategy, including thalidomide and its derivatives that bind to the substrate recognition receptor cereblon (CRBN), and anticancer sulfonamides that target DCAF15 to suppress the neoplastic proliferation of multiple myeloma and colorectal cancers, respectively. To this end, PROTACs have been developed as a group of engineered bi-functional chemical glues that induce the ubiquitination-mediated degradation of substrates via recruiting E3 ligases, such as CRL4 (CRBN) and CRL2 (pVHL). We summarize the recent major advances in the CRL4 research field towards understanding its involvement in tumorigenesis and further discuss its clinical implications. The anti-tumor effects using the PROTAC approach to target the degradation of undruggable targets are also highlighted. |
DOI | 10.1016/j.bbcan.2018.11.007 |
Alternate Journal | Biochim Biophys Acta Rev Cancer |
PubMed ID | 30602127 |
PubMed Central ID | PMC7179951 |
Grant List | R01 GM094777 / GM / NIGMS NIH HHS / United States R01 CA213992 / CA / NCI NIH HHS / United States K01 AG052627 / AG / NIA NIH HHS / United States R01 CA177910 / CA / NCI NIH HHS / United States R01 CA159925 / CA / NCI NIH HHS / United States |
Related Faculty:
Pengbo Zhou, Ph.D.