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

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.

SUBMITTER: He L

PROVIDER: S-EPMC8463077 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description:This SuperSeries is composed of the SubSeries listed below.

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

Project description:The YAP and TAZ paralogues, the ultimate effectors of the Hippo signaling pathway, are deregulated in many cancer types. They are transcriptional co-activators that are recruited to their target sites, primarily by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB and STAT3, key factors that mediate an epigenetic switch linking inflammation to breast cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain that is important for transformation, co-occupy many target sites in vivo via the sequence motifs of AP-1 and (to a lesser extent) STAT3, and stimulate transcriptional activation by AP-1 proteins. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes. YAP/TAZ, JUNB, and STAT3 directly regulate a common set of target genes that overlap, but are distinct from, those regulated by YAP/TAZ and TEADs. The set of target genes regulated by YAP/TAZ, STAT3, and JUNB is associated with poor survival in breast cancer patients with the triple-negative form of the disease.

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

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

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Project description:YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation (RNA-seq)

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

Project description:YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation (ChIP-seq)

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The YAP/TAZ transcriptional co-activators have opposing effects at different stages of osteoblast differentiation.

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Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma.

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