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Merlin, a multi‐suppressor from cell membrane to the nucleus
Author(s) -
Zhou Lu,
Hanemann C. Oliver
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.03.016
Subject(s) - merlin (protein) , microbiology and biotechnology , ubiquitin ligase , receptor tyrosine kinase , biology , pi3k/akt/mtor pathway , mapk/erk pathway , signal transduction , neurofibromatosis type 2 , cancer research , ubiquitin , suppressor , gene , neurofibromatosis , genetics
Recent evidence suggests that the neurofibromatosis type 2 ( NF2 ) gene encoded protein merlin suppresses mitogenic signalling not only at the cell membrane but also in the nucleus. At the membrane, merlin inhibits signalling by integrins and tyrosine receptor kinases (RTKs) and the activation of downstream pathways, including the Ras/Raf/MEK/ERK, FAK/Src, PI3K/AKT, Rac/PAK/JNK, mTORC1, and Wnt/β‐catenin pathways. In the nucleus, merlin suppresses the E3 ubiquitin ligase CRL4 DCAF1 to inhibit proliferation. Gene expression analysis suggested that CRL4 DCAF1 could also regulate the expression of integrins and RTKs. In this review, we explore the links between merlin function at the membrane and in the nucleus, and discuss the potential of targeting the master regulator CRL4 DCAF1 to treat NF2 and other merlin‐deficient tumours.