YES1

YAP1 (Yes-associated protein 1) is a transcriptional co-activator and a key regulator of the Hippo signaling pathway, which is crucial for controlling organ size, cell proliferation, and apoptosis. YAP1 is encoded by the YAP1 gene in humans and is involved in various cellular processes, including development, tissue regeneration, and cancer.

Structure

YAP1 is a protein that contains several important domains:

• The TEAD-binding domain, which allows YAP1 to interact with TEAD transcription factors.
• The WW domain, which mediates protein-protein interactions by binding to proline-rich motifs.
• The SH3-binding motif, which is involved in interactions with SH3 domain-containing proteins.
• The PDZ-binding motif, which allows interaction with PDZ domain-containing proteins.

Function

YAP1 functions primarily as a transcriptional co-activator. It does not bind DNA directly but interacts with transcription factors such as TEAD to regulate gene expression. YAP1 activity is regulated by the Hippo signaling pathway, which controls its localization and stability.

Role in the Hippo Pathway

In the Hippo pathway, YAP1 is phosphorylated by the LATS1/2 kinases, leading to its retention in the cytoplasm and subsequent degradation. When the Hippo pathway is inactive, YAP1 translocates to the nucleus, where it interacts with TEAD transcription factors to promote the expression of genes involved in cell proliferation and survival.

Clinical Significance

YAP1 is implicated in various diseases, particularly cancer. Overexpression or hyperactivation of YAP1 has been observed in several types of cancer, including liver, breast, and colorectal cancers. YAP1 promotes tumor growth and metastasis by enhancing cell proliferation and inhibiting apoptosis.

YAP1 in Cancer

YAP1 acts as an oncogene in many cancers. Its overactivity can lead to uncontrolled cell growth and resistance to cell death, contributing to tumorigenesis. Targeting YAP1 and its interactions is a potential therapeutic strategy in cancer treatment.

Research and Therapeutic Potential

Research on YAP1 is ongoing to better understand its role in development and disease. Inhibitors of YAP1-TEAD interaction are being explored as potential cancer therapies. Additionally, YAP1 is being studied for its role in tissue regeneration and repair.

Also see

• Hippo signaling pathway
• TEAD transcription factors
• Cell proliferation
• Apoptosis
• Oncogene