The YAP and TAZ transcriptional co-activators are WW domain containing proteins negatively regulated by the Hippo tumor suppressor pathway.Krüppel-like factor 5 (KLF5) is a PY motif-containing transcription factor highly expressed in ER/PR/HER2 triple ncgative breast cancers.KLF5 promotes breast cell proliferation partially through a downstream gene,fibroblast growth factor binding protein 1 (FGF-BP).The KLF5 protein is ubiquitinated by WWP 1 and SCFFbw7 E3 ligases and degraded by the proteasome.We demonstrated that the YAP and TAZ transcriptional co-activators upregulated the KLF5 expression through antagonizing the WWP1-, but not Fbw7-, mediated, KLF5 ubiquitination and degradation.