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- Title
Opposing roles of angiomotin-like-1 and zona occludens-2 on pro-apoptotic function of YAP.
- Authors
Oka, T; Schmitt, A P; Sudol, M
- Abstract
YAP (Yes-associated protein) oncogene has been found to form a stable complex with members of the Angiomotin (Amot) family of proteins, which bind WW domains of YAP and sequester the protein in the cytoplasm and junctional complexes. The Amot-mediated retention of YAP in the cytoplasm results in the inhibition of its proliferative function. Using apoptotic 'read-out' of YAP in HEK293 cells, we confirmed the molecular mode by which Amot regulates YAP. We showed that a representative member of the Amot family, AmotL1 (Angiomotin-like-1), uses its PPxY motifs to bind WW domains of YAP and inhibit YAP's nuclear translocation and pro-apoptotic function. Recently we also showed that YAP uses its PDZ-binding motif to interact with zona occludens-2 (ZO-2) protein, which promotes YAP's translocation to the nucleus. We also asked if AmotL1, YAP and ZO-2 signal together. We report here that AmotL1 and ZO-2 form a tripartite complex with YAP and regulate its function in HEK293 cells in opposite directions. AmotL1 inhibits pro-apoptotic function of YAP, whereas ZO-2 enhances it. As YAP is a potent oncogene, the identification and characterization of its regulators is important. AmotL1 and ZO-2 are two candidates that could be harnessed to control the oncogenic function of YAP.
- Subjects
APOPTOSIS; ONCOGENES; CANCER cell proliferation; CYTOPLASM; JUNCTIONAL complexes (Epithelium); CCN intercellular signaling proteins; PROTEIN binding
- Publication
Oncogene, 2012, Vol 31, Issue 1, p128
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2011.216