F-box only protein 42 (FBXO42)

**F-box only protein 42 (FBXO42)** is a substrate recognition component of the SCF (SKP1–CUL1–F-box protein) E3 ubiquitin ligase complex, responsible for targeting specific proteins for ubiquitination and proteasomal degradation[3][4]. FBXO42 recognizes and facilitates the polyubiquitination of several substrates including p53/TP53, RBPJ (a Notch pathway transcriptional regulator), and p57Kip2 (CDKN1C), among others[1][2][3]. Through this activity, FBXO42 plays crucial roles in cell cycle regulation, chromatin remodeling, transcriptional regulation, and cellular proliferation. It is implicated in the pathogenesis of various cancers, including T cell acute lymphoblastic leukemia (T-ALL), hepatocellular carcinoma, glioblastoma, and neuroblastoma. Inhibition or loss of FBXO42 activity impairs Notch signaling, reduces tumor cell invasiveness, and affects cell cycle control[1][2]. It is considered a promising target for cancer therapeutics, and investigational agents like MLN4924 that impair the function of the SCF complex are being explored for therapeutic intervention[1].

Other names

F-box protein 42FBX42JFKKIAA1332Just one F-box and Kelch domain-containing protein

Inhibition of SCF E3 ligase activity (MLN4924 inhibits neddylation of cullin-RING ligases, affecting FBXO42 function)