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J Biol Chem. 2009 May 22;284(21):14347-58. doi: 10.1074/jbc.M901568200. Epub 2009 Mar 26.

TEADs mediate nuclear retention of TAZ to promote oncogenic transformation.

Author information

1
Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, Singapore 138673, Singapore.

Abstract

The transcriptional coactivators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. The expression level of TAZ is recently shown to be elevated in invasive breast cancer cells and some primary breast cancers. TAZ is important for breast cancer cell migration, invasion, and tumorigenesis, but the underlying mechanism is not defined. In this study, we show that TAZ interacts with TEAD transcriptional factors. Knockdown of TEADs suppresses TAZ-mediated oncogenic transformation of MCF10A cells. Uncoupling TAZ from Hippo regulation by S89A mutation enhances its transforming ability. Several residues located in the N-terminal region of TAZ are identified to be important for interaction with TEADs, and these same residues are equally important for TAZ to transform MCF10A cells. Mechanistically, TAZ mutants defective in interaction with TEADs fail to accumulate in the nucleus. Live cell imaging of enhanced green fluorescent protein-TAZ and its mutant defective in TEAD interaction suggests that TEAD interaction mediates nuclear retention. These results reveal a novel mechanism for TEADs to regulate nuclear retention and thus the transforming ability of TAZ.

PMID:
19324876
PMCID:
PMC2682883
DOI:
10.1074/jbc.M901568200
[Indexed for MEDLINE]
Free PMC Article

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