YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation

eLife

Kevin Struhl¹  Lizhi He¹  Fengxiang Wei²  Henry Pratt³  Zhiping Weng³  Mingshi Gao³ 

[1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States;Genetics Laboratory, Shenzhen Longgang District Maternity and Child Healthcare Hospital, Shenzhen, China;Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States;

关键词: transcriptional co-activator;    cellular transformation;    gene regulation;    YAP;    TAZ;    cancer;    Human;   

DOI  :  10.7554/eLife.67312

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY