Role of Angiomotin-like 2 mono-ubiquitination on YAP inhibition

Title
Role of Angiomotin-like 2 mono-ubiquitination on YAP inhibition
Authors
이철주김민주김민철박성준임대식
Issue Date
2016-01
Publisher
EMBO reports
Citation
VOL 17, NO 1-78
Abstract
LATS1/2 (large tumor suppressor) kinases and the Angiomotin family proteins are potent inhibitors of the YAP (yes-associated protein) oncoprotein, but the underlying molecular mechanism is not fully understood. Here, we report for the first time that USP9X is a deubiquitinase of Angiomotin-like 2 (AMOTL2) and that AMOTL2 mono-ubiquitination is required for YAP inhibition. USP9X knockdown increased the LATS-mediated phosphorylation of YAP and decreased the transcriptional output of YAP. Conversely, overexpression of USP9X reactivated YAP in densely cultured cells. Both genetic and biochemical approaches identified AMOTL2 as a target of USP9X. AMOTL2 was found to be ubiquitinated at K347 and K408, which both reside in the protein's coiled-coil domain. The AMOTL2 K347/408R mutant, which cannot be ubiquitinated, was impaired in its ability to inhibit YAP. Furthermore, ubiquitinated AMOTL2 can bind to the UBA domain of LATS kinase, and this domain is required for the function of LATS. Our results provide novel insights into the activation mechanisms of core Hippo pathway components.
URI
http://pubs.kist.re.kr/handle/201004/66565
ISSN
1469-221X
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KIST Publication > Article
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