Binding of the transcriptional co-activator, YAP1, to the transcription factor Oct4, induces Sox2, which is a transcription actor necessary for the self-renewal of stem-like cells from non-small cell lung cancer. The WW domain of YAP1 binds to the PPxY motif of Oct4 to induce Sox2. Delivering a peptide corresponding to the WW domain could prevent the induction of Sox2 and stemness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit stemness. Disclosed are compounds that affect the Yap1:Oct4 interaction.
转录共激活因子YAP1与转录因子Oct4的结合会诱导Sox2的表达,Sox2是从非小细胞肺癌干细胞中必需的转录因子。YAP1的WW结构域与Oct4的P
PxY基序结合可诱导Sox2的表达。提供了相应的WW结构域肽段可预防Sox2和干性的诱导。同样,P
PxY基序的肽段和类似物也能抑制干性。揭示了影响Yap1:Oct4相互作用的化合物。