RuvB-like AAA ATPase 1 and 2 (RuvBL1/2)

RuvB-like AAA ATPase 1 (RuvBL1) and RuvB-like AAA ATPase 2 (RuvBL2) are highly conserved members of the AAA+ ATPase superfamily that typically function as a heterohexameric or heterododecameric complex [1.1.1, 1.2.4]. They serve as essential scaffolds and co-chaperones for the assembly and maturation of numerous multiprotein complexes, including the R2TP/PAQosome, TIP60, and INO80, which are critical for chromatin remodeling, DNA repair, and the stability of PIKK family kinases like ATR and ATM [1.2.2, 1.2.3]. In many cancers, RuvBL1/2 are overexpressed and act as vital cofactors for oncogenic transcription factors such as MYC and beta-catenin, facilitating the expression of genes required for rapid cell proliferation and survival [1.1.1, 1.3.4]. Pharmacological inhibition of their ATPase activity, notably by small molecules like CB-6644, has demonstrated potent anti-tumor effects in preclinical models of neuroblastoma, lung cancer, and lymphoma by inducing S-phase arrest and replication catastrophe [1.1.2, 1.2.2]. Despite their promise as therapeutic targets, the broad essentiality of RuvBL1/2 in normal cellular homeostasis poses a significant challenge in achieving a sufficient therapeutic window for clinical application [1.2.1, 1.2.2]. High expression levels of these proteins are frequently associated with poor patient prognosis and may serve as valuable biomarkers for identifying high-risk disease states [1.4.1, 1.4.2].

Other names

PontinReptinTIP49TIP48Rvb1Rvb2TIH1TIH2ECP54ECP51TAP54TAP51Pontin/ReptinTIP49/TIP48RuvB-like 1RuvB-like 2

Pharmacological inhibition of the ATPase activity of the RuvBL1/2 complex, which disrupts the assembly and maturation of essential multiprotein complexes like the PAQosome and reduces the activity of oncogenic transcription factors such as MYC.