Understanding WWTR1: A Non-Coding RNA Molecule with Potential as A Drug Target

Target Name: WWTR1

NCBI ID: G25937

WWTR1

Understanding WWTR1: A Non-Coding RNA Molecule with Potential as A Drug Target

Worldwide, approximately 17% of the human genome consists of non-coding RNA (ncRNA), which play a crucial role in various cellular processes. Among these ncRNAs, transcriptional co-activator with PDZ-binding motif (WWTR1) is a key regulator of gene expression and has been implicated in numerous diseases. In this article, we will explore the biology of WWTR1, its potential as a drug target, and its current status in the scientific literature.

Biogenesis and Structure

WWTR1, also known as heat shock factor 1 (HSF-1), is a non-coding RNA molecule that plays a vital role in the regulation of gene expression. It is expressed in a variety of tissues and cell types and is highly conserved across different species. WWTR1 has a unique structure that consists of a 193-amino acid protein domain and a non-coding RNA domain with a PDZ-binding motif (PZBM) at its C-terminus.

The PDZ-binding motif is a conserved motif that is found in various proteins, including transcription factors, and is involved in protein-protein interactions. It is composed of a unique set of amino acids that form a distinct structural motif that can interact with other proteins. PDZBM is responsible for the formation of a stable complex with the protein CoRQ3, which leads to the regulation of gene expression.

Function and Druggability

WWTR1 is a key regulator of gene expression and has been involved in numerous cellular processes. It plays a role in the regulation of DNA replication, cell growth, apoptosis, and stress response. Studies have shown that WWTR1 is highly expressed in various tissues and cell types, including the brain, heart, and liver. It is also involved in the regulation of inflammation, pain perception, and addiction.

Due to its unique structure and the involvement of PDZBM, WWTR1 has great potential as a drug target. The use of small molecules and antibodies to modulate WWTR1 activity has been shown to be effective in various cellular processes. For example, small molecules such as DMARDs (drugs that mimic organic compounds) and JNJ-4645, have been shown to inhibit the activity of WWTR1 and decrease the expression of its target genes. Similarly, antibodies against WWTR1 have been shown to reduce the activity of the protein and decrease the expression of its target genes.

Expression and Disease

WWTR1 has been shown to be involved in the development and progression of various diseases. For example, studies have shown that high expression of WWTR1 is associated with poor prognosis in various cancer types, including breast, ovarian, and colorectal cancer. Similarly, the expression of WWTR1 has been shown to be involved in the development of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

In addition to its involvement in disease, WWTR1 has also been shown to be involved in the regulation of normal cellular processes. For example, studies have shown that WWTR1 is involved in the regulation of cell cycle progression and apoptosis. It plays a role in the Regulation of protein stability and is involved in the degradation of damaged proteins.

Conclusion

In conclusion, WWTR1 is a non-coding RNA molecule that plays a crucial role in the regulation of gene expression and has been involved in numerous cellular processes. Its unique structure and the involvement of PDZBM make it a promising target for small molecules and antibodies. The expression of WWTR1 has been shown to be involved in the development and progression of various diseases, including cancer and neurodegenerative diseases. Further research is needed to fully understand the biology of WWTR1 and its potential as a drug target.

Protein Name: WW Domain Containing Transcription Regulator 1

Functions: Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:11118213, PubMed:18227151). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018)

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