论文部分内容阅读
INTRODUCTIONrnYAP (yes?associated protein) is a transcriptional cofactor that is highly related to TAZ (transcriptional co?activator with PDZ binding motif). Both YAP and TAZ interact with TEA domain (TEAD) containing family transcriptional factors to induce gene transcription for diverse cellular processes, including cell prolifera?tion and differentiation.1–6 Both YAP and TAZ are negatively regulated by the Hippo pathway, a conserved pathway that regulates organ size and tumorigenesis.2,5–6 Upon stimulation of the Hippo pathway, YAP is phosphorylated, which undergoes protein degradation or interaction with 14?3?3 for YAP cytoplasmic retention.1–6 When dephosphorylated, YAP enters nuclei and interacts with TEAD family transcriptional factors to induce gene expression.1–6 Recent studies indicate that, in addition to the Hippo pathway, YAP appears to be an integrator for cell proliferation and differentiation in response to various extracel?lular factors, including cell adhesion?driven mechanical cellular stress,7 bone morphogenetic proteins (BMPs),1,8 and Wnts.4,9 In addition to be a co?activator for TEAD family proteins, it serves as a co?regulator for other transcriptional factors that are crucial for bone homeostasis, such as phospho?Smad1/5/8,8,10 RUNX2,11 peroxisome proliferator?activated receptor?γ (PPARγ),2 signal transducer and activator of transcription factor 3 (STAT3),12 and β?catenin.9 Thus it is likely that YAP plays a role in bone homeostasis.