Open AccessBRCA1/BARD1-dependent ubiquitination of NF2 regulates Hippo-YAP1 signaling
Author(s) -
Sachin Kumar Verma,
Narayana Yeddula,
Yasushi Soda,
Quan Zhu,
Gerald M. Pao,
James J. Moresco,
Jolene K. Diedrich,
Audrey Hong,
Steve Plouffe,
Toshiro Moroishi,
KunLiang Guan,
Inder M. Verma
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1822155116
Subject(s) - yap1 , hippo signaling pathway , microbiology and biotechnology , ubiquitin , carcinogenesis , signal transduction , biology , cell growth , dna damage , chromatin , ubiquitin ligase , dna repair , cancer research , transcription factor , dna , genetics , cancer , gene
Significance Normal cells harbor protective mechanisms to sense DNA damage, halt cell growth, and repair chromatin lesions to maintain genomic stability. How mitogen signaling in proliferating cells is affected upon BRCA1 loss as part of these protective checkpoints is an intriguing question. This study reveals a unique finding of linking BRCA1 to Hippo signaling pathway to explain this conundrum. Our work shows that serum-responsive expression of BRCA1 is required for YAP1 stability. Ubiquitination of NF2 by BRCA1/BARD1 in proliferating cells inhibits NF2/LATS association and Hippo signaling. These findings suggest Hippo signaling activation as a protective barrier in BRCA1-deficient cells, which upon inactivation, promotes cell proliferation and tumorigenesis.
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