Merlin/NF2 loss-driven tumorigenesis linked to CRL4DCAF1-mediated inhibition of the hippo pathway kinases lats1 and 2 in the nucleus Journal Article

   

Authors:	Li, W.; Cooper, J.; Zhou, L.; Yang, C.; Erdjument-Bromage, H.; Zagzag, D.; Snuderl, M.; Ladanyi, M.; Hanemann, C.; Zhou, P.; Karajannis, M.; Giancotti, F.
Article Title:	Merlin/NF2 loss-driven tumorigenesis linked to CRL4DCAF1-mediated inhibition of the hippo pathway kinases lats1 and 2 in the nucleus
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 CRL4DCAF1 in the nucleus. We found that derepressed CRL4DCAF1 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 CRL4DCAF1 promotes activation of YAP by inhibiting Lats1 and 2 in the nucleus. © 2014 Elsevier Inc.
Journal Title:	Cancer Cell
Volume:	26
Issue:	1
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2014-07-14
Start Page:	48
End Page:	60
Language:	English
DOI:	10.1016/j.ccr.2014.05.001
PROVIDER:	scopus
PUBMED:	25026211
PMCID:	PMC4126592
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84904266769&partnerID=40&md5=61898623fbf42a3ae366cd48a824b26f
Notes:	Export Date: 1 August 2014 -- CODEN: CCAEC -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/55069