Wilms' tumor 1-associating protein (WTAP) (WTAP)

Wilms' tumor 1-associating protein (WTAP) is a ubiquitously expressed nuclear protein that serves as a critical regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex (UniProt, 2024). It functions by recruiting the catalytic components METTL3 and METTL14 to nuclear speckles, thereby facilitating the most prevalent internal modification of eukaryotic mRNA (PubMed, 2019). Beyond its role in the 'm6A writer' complex, WTAP is involved in pre-mRNA splicing, cell cycle regulation (particularly the G2/M transition), and X-chromosome inactivation (Wikipedia, 2024). In oncology, WTAP is frequently overexpressed and functions as an oncogene in various malignancies, including acute myeloid leukemia (AML), hepatocellular carcinoma (HCC), and diffuse large B-cell lymphoma (DLBCL), where it promotes cell proliferation and drug resistance (NIH, 2022). It has also been implicated in inflammatory conditions such as psoriasis and periodontitis (NIH, 2026). While no direct WTAP inhibitors are currently approved, it is an active area of research for targeted therapy, with studies exploring its modulation via Hsp90 inhibitors or through the inhibition of its downstream signaling effectors like Fak and AKT (MDPI, 2023). Genetic studies indicate that WTAP is essential for embryonic development, as its deficiency leads to early embryonic lethality (PNAS, 2006).

Other names

WT1-associated proteinMum2Female-lethal(2)D homologWT1-associating proteinhFL(2)D

WTAP acts as a regulatory subunit of the m6A methyltransferase complex, recruiting METTL3 and METTL14 to target RNAs. Drugs targeting WTAP-related pathways aim to inhibit its stabilization (e.g., via Hsp90 inhibition) or block downstream oncogenic signaling (e.g., ERK, AKT, or Fak pathways) to overcome drug resistance and inhibit tumor growth (NIH, 2022; MDPI, 2023).