WD repeat-containing protein 77 (WDR77) (WDR77)

WD repeat-containing protein 77 (WDR77), also known as MEP50, is a critical non-catalytic component of the methylosome complex, serving as an essential cofactor for the protein arginine methyltransferase 5 (PRMT5) (UniProt Q9BQA1) [1]. It facilitates the assembly of the PRMT5-WDR77 hetero-octameric complex, which is responsible for the symmetric dimethylation of arginine residues on various histone and non-histone proteins, including Sm proteins involved in RNA splicing (PMID: 12167634) [2]. Beyond its role in the methylosome, WDR77 acts as a transcriptional coactivator for nuclear receptors such as the androgen receptor and estrogen receptor, thereby influencing gene expression programs linked to cell growth (PMID: 17525332) [3]. In oncology, WDR77 is frequently overexpressed and is considered a driver of tumorigenesis in cancers such as lung, prostate, and breast cancer (PMID: 26307174) [4]. Therapeutic strategies primarily focus on inhibiting the PRMT5-WDR77 complex activity, particularly in the context of MTAP-deleted tumors where cells exhibit a specific vulnerability to PRMT5 inhibition (PMID: 26912361) [5]. While direct inhibitors of WDR77 are less common than those targeting the PRMT5 catalytic site, the stability and function of the entire complex are vital for the efficacy of current PRMT5-targeted therapies like AMG 193 and MRTX1719 [6].

Other names

MEP50Methylosome protein 50p44HKMT1069WD repeat protein 77

Inhibition of the PRMT5-WDR77 methyltransferase complex activity