WT1

Fig1. WT1 is an important factor for AML maintenance in multiple subtypes. (Sandeep Potluri, 2021)

What is WT1 protein?

WT1 (WT1 transcription factor) gene is a protein coding gene which situated on the short arm of chromosome 11 at locus 11p13. The WT1 gene is normally expressed in fetal kidney and mesothelioma. WT1, the product of WT1 gene, is a nuclear protein with structural motifs characteristic of transcription factors, including four C-terminal zinc fingers. While different pre-mRNA processing could result in 16 isoforms of the protein, the inclusion or exclusion of exon 5 and three amino acids (KTS) between zinc fingers 3 and 4 largely affects the activity of the WT1 protein. The WT1 protein is consisted of 449 amino acids and its molecular mass is approximately 49.2 kDa.

What is the function of WT1 protein?

WT1 is a transcription factor that plays an important role in cellular development and cell survival. With the inclusion of exon 5, WT-1 (+KTS) binds to both DNA and RNA and is RNase but not DNase sensitive. This form also colocalizes with splicing factor in a speckled nuclear particle, suggesting that WT-1 protein may function as both a transcription factor and a splicing regulator. At the same time, it has a tumor suppressor as well as an oncogenic role in tumor formation.

WT1 Related Signaling Pathway

The protein encoded by WT1 gene is a bidirectional transcription factor, which has dual functions of inhibiting tumor growth and activating oncogene transcription. WT1 may negatively regulate the Wnt/β-catenin signaling pathway, and is also regulated by many signaling pathways, such as PI3K/Akt and MAPK/ERK signaling pathways. It is also involved in transcriptional regulation of some genes as a transcription factor.

WT1 Related Diseases

Wilm's tumor (WT1) is associated with mutations of WT1, a zinc-finger transcription factor that is essential for the development of the metanephric kidney and the urogenital system. Mutations in the WT1 gene are also associated with frasier syndrome (FS). FS is an X-linked genetic disorder in which mutations in the WT1 gene cause tubular dysplasia and gonadal hypoplasia. Other related diseases include: nephroblastoma, skeletal system diseases, reproductive system diseases, etc. In addition, it is highly expressed in all types of solid tumors and leukemias, especially acute myeloid leukemia (AML).

Bioapplications of WT1

WT1 can be used as a tumor marker to diagnose and monitor the effect of tumor therapy. In addition, anti-sense oligonucleotides, siRNA and other drugs targeting WT1 are also being studied and are expected to become a new tumor therapy.

Case Study 1: Chunhong Wang, 2022

Fig1. Overexpression of miR-671-5p impairs but knockdown of miR-671-5p protects podocyte integrity in vitro.

Case Study 2: Zhuna Wu, 2023

Fig2. Significantly high WT1 expression was observed in cervical caner tissues with relapse.

WT1 has several biochemical functions, for example, C2H2 zinc finger domain binding,RNA binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by WT1 itself. We selected most functions WT1 had, and list some proteins which have the same functions with WT1. You can find most of the proteins on our site.

WT1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with WT1 here. Most of them are supplied by our site. Hope this information will be useful for your research of WT1.

KRTAP10-8;KRT40;DVL3;NPM3;ZNF205;DIRAS3;NAT2;CCL5;KLK7;MDM2;TAOK1;CASZ1;THRSP