WDR5

What is WDR5 protein?

WDR5 gene (WD repeat domain 5) is a protein coding gene which situated on the long arm of chromosome 9 at locus 9q34. This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 7 WD repeats. The WDR5 protein is consisted of 334 amino acids and WDR5 molecular weight is approximately 36.6 kDa.

What is the function of WDR5 protein?

The WDR5 protein is a highly conserved WD40 repeat protein that plays a critical regulatory role in a variety of cellular processes. The most typical function of WDR5 is as the core scaffold component of the histone methyltransferase complex, especially for the methylation of lysine at the fourth position of histone H3, which is closely related to the transcriptional activation of the gene. In addition, WDR5 is involved in processes that control the integrity of cell division. WDR5 is involved in the regulation of gene expression in the nucleus through interactions with a variety of proteins and long non-coding Rnas, including as a component of a variety of histone modification complexes, as well as direct interactions with specific transcription factors.

Fig1. Schematic illustration of WDR5 function in neuroblastoma tumorigenesis. (Qi-lei Han, 2022)

WDR5 related signaling pathway

The WDR5 protein plays multiple roles in signal transduction and is a key regulator of histone methylation modification, particularly during the methylation of histone H3K4. WDR5 promotes transcriptional activation of genes by interacting with the histone methyltransferase complex of the MLL family. In addition, WDR5 also interacts with N-myc protein to form a transcription complex, which plays an important role in the occurrence and development of tumors such as neuroblastoma. WDR5 is also involved in the regulation of cell cycle and DNA replication. The study showed that inhibitors of WDR5 can affect the expression of several genes, including protein synthesis genes, which are closely related to cell growth, proliferation, and survival.

WDR5 related diseases

The WDR5 protein has been implicated in a variety of diseases, and it plays a variety of biological roles within cells. WDR5 is closely associated with the development of neuroblastoma because it is a component of the histone methyltransferase complex. WDR5 is also involved in other types of cancer, including breast and prostate cancer. In addition, dysfunction in WDR5 has been linked to rare diseases such as Noonan syndrome and multiple sclerosis. The latest study also found that WDR5 may be linked to Alzheimer's disease because WDR5 plays an important role in maintaining metabolic and cognitive function in the brain.

Bioapplications of WDR5

The WDR5 protein has an important role in biomedical applications, especially in the field of cancer therapy. The abnormal expression of WDR5 in a variety of tumors is closely related to the occurrence and development of tumors, so it becomes a potential target for cancer therapy. Researchers are developing small molecule inhibitors that target WDR5, which inhibit the proliferation of tumor cells by interfering with the function of WDR5, and are expected to become new anticancer drugs. In addition, inhibitors of WDR5 can also be used in combination with other drugs to produce synergistic effects and enhance anti-tumor effects. These studies provide a new perspective and strategy for the application of WDR5 in the biomedical field.