Abstract
Mammals express four highly conserved TEAD/TEF transcription factors that bind the same DNA sequence, but serve different functions during development. TEAD-2/TEF-4 protein purified from mouse cells was associated predominantly with a novel TEAD-binding domain at the amino terminus of YAP65, a powerful transcriptional coactivator. YAP65 interacted specifically with the carboxyl terminus of all four TEAD proteins. Both this interaction and sequence-specific DNA binding by TEAD were required for transcriptional activation in mouse cells. Expression of YAP in lymphocytic cells that normally do not support TEAD-dependent transcription (e.g., MPC11) resulted in up to 300-fold induction of TEAD activity. Conversely, TEAD overexpression squelched YAP activity. Therefore, the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors. However, whereas TEAD was concentrated in the nucleus, excess YAP65 accumulated in the cytoplasm as a complex with the cytoplasmic localization protein, 14-3-3. Because TEAD-dependent transcription was limited by YAP65, and YAP65 also binds Src/Yes protein tyrosine kinases, we propose that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 8 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 15, 2021, 10:40 a.m.) |
Indexed | 1 day, 15 hours ago (Sept. 4, 2025, 9:22 a.m.) |
Issued | 24 years, 3 months ago (May 15, 2001) |
Published | 24 years, 3 months ago (May 15, 2001) |
Published Online | 24 years, 3 months ago (May 15, 2001) |
Published Print | 24 years, 3 months ago (May 15, 2001) |
@article{Vassilev_2001, title={TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm}, volume={15}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.888601}, DOI={10.1101/gad.888601}, number={10}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Vassilev, Alex and Kaneko, Kotaro J. and Shu, Hongjun and Zhao, Yingming and DePamphilis, Melvin L.}, year={2001}, month=may, pages={1229–1241} }