University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences

Publication Date

2021-08-31

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Genetics and Genomics | Neoplasms

Abstract

The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observation and differences in relative crosslinking efficiencies of JUNB, TEAD, and STAT3 at YAP/TAZ target sites suggest that YAP/TAZ is recruited by different forms of an AP-1/STAT3/TEAD complex depending on the recruiting motif. The different classes of YAP/TAZ target sites are associated with largely non-overlapping genes with distinct functions. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes from shared YAP/TAZ target sites. Genes containing either the AP-1 or TEAD class of YAP/TAZ sites are associated with poor survival of breast cancer patients with the triple-negative form of the disease.

Keywords

TAZ, YAP, cancer, cancer biology, cellular transformation, chromosomes, gene expression, gene regulation, human, transcriptional co-activator

Rights and Permissions

Copyright © 2021, He et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.67312

Source

He L, Pratt H, Gao M, Wei F, Weng Z, Struhl K. YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation. Elife. 2021 Aug 31;10:e67312. doi: 10.7554/eLife.67312. PMID: 34463254; PMCID: PMC8463077. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

eLife

PubMed ID

34463254

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS