⑴Binding to TEAD
YAP and TAZ do not have DNA binding domains, and they need to bind transcription factors to enter DNA. YAP/TAZ mainly utilizes the TEAD family of transcription factors to induce most of its biologically relevant gene expression programs [15,16]. Under favorable conditions, YAP and TAZ actively promote cell growth through a transcriptional program mediated by TEAD family transcription factors[10]. Through these factors, YAP/TAZ binds to DNA and co-occupies chromatin with activin-1 (AP-1, JUN and FOS protein dimers) at complex cis-regulatory elements containing TEAD and AP-1 motifs. YAP/TAZ/TEAD and AP-1 form a complex that synergistically activates target genes directly involved in the control of S-phase entry and mitosis. The AP-1 transcription factor, one of the most well-characterized immediate early gene products, is formed by dimerization of Fos family proteins (Fos, FOSB, FRA1 and FRA2) and Jun family proteins (Jun, JUNB and JUND) [17]. As a heterodimer, AP-1 binds to the promoter regions of specific target genes and translates extracellular signals into changes in gene expression[18]. Upon activation, YAP/TAZ translocates into the nucleus and binds to TEAD transcription factors, interacts with chromatin remodeling factors, and regulates RNA polymerase II (Pol II) to drive or repress the expression of target genes and promote the transcriptional program. Proliferation or cell specificity mainly includes the cell cycle, cell migration and cell fate regulators[18,19]. Interestingly, the YAP/TAZ-TEAD complex can be disrupted by two very different mechanisms, one of which is the direct inhibition of TEAD-binding protein fragments: Ω-loop or α-helix[11], and the other is the formation of complexes with YAP/TAZ by other substances to replace the association between YAP/TAZ and the DNA binding platform TEAD. A study found that ARID1A-SWI/SNF complexes precisely inhibit the transcriptional coactivator YAP/TAZ through ARID1A-mediated YAP/TAZ and SWI/SNF complexes [20,21].