| Literature DB >> 25026211 |
Wei Li1, Jonathan Cooper2, Lu Zhou3, Chenyi Yang4, Hediye Erdjument-Bromage5, David Zagzag6, Matija Snuderl6, Marc Ladanyi7, C Oliver Hanemann3, Pengbo Zhou4, Matthias A Karajannis8, Filippo G Giancotti9.
Abstract
It is currently unclear whether Merlin/NF2 suppresses tumorigenesis by activating upstream components of the Hippo pathway at the plasma membrane or by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. We found that derepressed CRL4(DCAF1) promotes YAP- and TEAD-dependent transcription by ubiquitylating and, thereby, inhibiting Lats1 and 2 in the nucleus. Genetic epistasis experiments and analysis of tumor-derived missense mutations indicate that this signaling connection sustains the oncogenicity of Merlin-deficient tumor cells. Analysis of clinical samples confirms that this pathway operates in NF2-mutant tumors. We conclude that derepressed CRL4(DCAF1) promotes activation of YAP by inhibiting Lats1 and 2 in the nucleus.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25026211 PMCID： PMC4126592 DOI： 10.1016/j.ccr.2014.05.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743