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

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, over-expression 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 cann

SUBMITTER: Kim M 

PROVIDER: S-EPMC4718409 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature