Importance of Cullin4 Ubiquitin Ligase in Malignant Pleural Mesothelioma.

ABSTRACT: Neurofibromatosis type 2 (NF2), the tumor suppressor frequently lost in malignant pleural mesothelioma (MPM), suppresses tumorigenesis in part by inhibiting the Cullin4 ubiquitin ligase (CUL4) complex in the nucleus. Here, we evaluated the importance of CUL4 in MPM progression and tested the efficacy of cullin inhibition by pevonedistat, a small molecule inhibiting cullin neddylation. CUL4 paralogs (CUL4A and CUL4B) were upregulated in MPM tumor specimens compared to nonmalignant pleural tissues. High gene and protein expressions of CUL4B was associated with a worse progression-free survival of MPM patients. Among 13 MPM cell lines tested, five (38%) were highly sensitive to pevonedistat (half maximal inhibitory concentration of cell survival IC₅₀ < 0.5 µM). This remained true i

SUBMITTER: Meerang M 

PROVIDER: S-EPMC7699720 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature