Siew Wee Chan1, Chun Jye Lim1, Yaan Fun Chong1, Ajaybabu Venkatesan Pobbati1, Caixia Huang1 and Wanjin Hong1,2.
1 - Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673.
2 - Department of Biochemistry, National University of Singapore.
Published in J. Biol. Chem., 11th January 2011. [Epub ahead of print]
The Hippo pathway restricts the activity of transcriptional coactivators TAZ and YAP by phosphorylating them for cytoplasmic sequestration or degradation. In this report, we describe an independent mechanism for the cell to restrict the activity of TAZ and YAP through interaction with angiomotin (Amot) and angiomotin-like 1 (AmotL1). Amot and AmotL1 were robustly co-immunoprecipitated with Flag-tagged TAZ and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of Amot. Amot and AmotL1 also interact with YAP via the first WW domain of YAP. Overexpression of Amot and AmotL1 caused cytoplasmic retention of TAZ and suppressed its transcriptional outcome such as the expression of CTGF and Cyr61. Hippo refractory TAZ mutant (S89A) is also negatively regulated by Amot and AmotL1. HEK293 cells express the highest level of Amot and AmotL1 among 9 cell lines examined and silencing the expression of endogenous Amot increased the expression of CTGF and Cyr61 either at basal or upon overexpression of exogenous S89A. These results reveal a novel mechanism to restrict the activity of TAZ and YAP through physical interaction with Amot and AmotL1.