MAML1/2 promote YAP/TAZ nuclear localization and tumorigenesis
Ji-Young Kim, Hyeryun Kwon, You Keun Shin, Gahyeon Song, Tae Bok Lee, Youngeun Kim, Wonyoung Jeong, Ukjin Lee, Xianglan Zhang, Gilyeong Nam, Hei‐Cheul Jeung, Wantae Kim, Eek‐hoon Jho
Abstract
Significance The Hippo-YAP/TAZ pathway plays pivotal roles in controlling tissue growth, and its abnormal regulation is frequently implicated in a variety of cancers. We have identified MAML1/2 as critical regulators for YAP/TAZ nuclear retention and transcription activities. Clinical analysis with specimens of a human cancer patient and a public cancer database reveals pathological association between MAML expression and YAP signature. Furthermore, our results suggest that the cell density governing YAP/TAZ subcellular localization can also function as an important intrinsic mechanism for miR30c-dependent regulation of MAML1 level. Our findings provide mechanistic insights of YAP/TAZ-dependent growth control pathway and tumorigenesis.