No abstract

TAZ promotes cell proliferation, development, and tumorigenesis by regulating target gene transcription. However, how TAZ orchestrates the transcriptional responses remains poorly defined. Here we demonstrate that TAZ forms nuclear condensates via liquid-liquid phase separation to compartmentalize its DNA binding co-factor TEAD4, the transcription co-activators BRD4 and MED1 and the transcription elongation factor CDK9 for activation of gene expression.TAZ, but not its paralog YAP, forms phase-separated droplets in vitro and liquid-like nuclear condensates in vivo, and this ability is negatively regulated by Hippo signaling via LATS-mediated phosphorylation and mediated by the coiled-coil domain. Deletion of the TAZ coiled-coil domain or substitution with the YAP coiled-coil domain does not affect the interaction of TAZ with its partners, but prevents its phase separation and more importantly, its ability to induce target gene expression. Thus, our study identifies a novel mechanism for the transcriptional activation by TAZ and demonstrates for the first time that pathway-specific transcription factors also engage the phase separation mechanism for efficient transcription activation.

The targeted delivery of chemotherapeutic drugs is amajor challenge in the clinical treatment of cancer.Herein, we constructed amultifunctional DNAnanoplatform as aversatile carrier of the highly potent platinum-based DNAintercalator, 56MESS.I no ur rational design, 56MESS was efficiently loaded into the double-bundle DNAt etrahedron through intercalation with the DNAd uplex. With the integration of an anobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNAn anocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapyw ithout obvious systemic toxicity. This DNA-based platinum-drug delivery system provides apromising strategy for the treatment of tumors.