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Review
, 51 (3), 126-133

DNA Binding Partners of YAP/TAZ

Affiliations
Review

DNA Binding Partners of YAP/TAZ

Min-Kyu Kim et al. BMB Rep.

Abstract

Hippo signaling plays critical roles in regulation of tissue homeostasis, organ size, and tumorigenesis by inhibiting YES-associated protein (YAP) and PDZ-binding protein TAZ through MST1/2 and LATS1/2 pathway. It is also engaged in cross-talk with various other signaling pathways, including WNT, BMPs, Notch, GPCRs, and Hedgehog to further modulate activities of YAP/TAZ. Because YAP and TAZ are transcriptional coactivators that lack DNA-binding activity, both proteins must interact with DNA-binding transcription factors to regulate target gene's expression. To activate target genes involved in cell proliferation, TEAD family members are major DNA-binding partners of YAP/TAZ. Accordingly, YAP/TAZ were originally classified as oncogenes. However, YAP might also play tumor-suppressing role. For example, YAP can bind to DNA-binding tumor suppressors including RUNXs and p73. Thus, YAP might act either as an oncogene or tumor suppressor depending on its binding partners. Here, we summarize roles of YAP depending on its DNA-binding partners and discuss context-dependent functions of YAP/TAZ. [BMB Reports 2018; 51(3): 126-133].

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Schematic diagram of YAP, TAZ, and Yki. P: Proline-rich region, TBD: TEAD-binding domain, SBD: Sd (Drosophila homolog of mammalian TEADs)-binding domain, WW: WW domain, C-C: coiled-coil region, TA: transactivation domain, PDZ BD: PDZ-binding domain.
Fig. 2
Fig. 2
Summary of signaling pathways that regulate interactions between YAP and its partners. SMADs activated by TGF-β translocate into the nucleus and bind to YAP, thus promoting the expression of target gene. TEAD is a representative transcription factor that binds to YAP and promotes cell proliferation. YAP is inactivated by LATS kinase which is activated by MST or inactivated by TRIO-RAC1 signaling. In DNA damage, YAP phosphorylated by c-ABL binds to p73 in the nucleus and promotes apoptosis. YAP-ERBB4 activated by NRG1 regulates cell growth by promoting the expression of target genes, including CTGF, CYR61, and ANKRD1.
Fig. 3
Fig. 3
Reciprocal regulation of YAP activity by TRIO-RAC1 signaling and the Hippo pathway. RUNX3 interacts with YAP and TEAD4 to form a YAP-TEAD4-RUNX3 ternary complex. When TRIO-RAC signaling is activated, kinase activity of LATS is inhibited while YAP activity is increased. RUNX3 then dissociates from the ternary complex, resulting in the formation YAP-TEAD complex. When cell growth is inhibited, TEAD dissociates from the ternary complex through LATS-mediated YAP phosphorylation, resulting in the formation YAP-RUNX3 complex. Therefore, LATS1/2-mediated YAP phosphorylation not only inhibits YAP-TEAD complex, but also facilitates YAP-RUNX3 complex formation.

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