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].