Ruvbl1, also known as Pontin/TIP49, is an evolutionary conserved protein belonging to the adenosine triphosphates associated with diverse cellular activities (AAA+) superfamily of ATPases. It forms a hetero-hexameric complex with Ruvbl2 and participates in multiple cellular processes such as chromatin remodeling, DNA damage repair, and the assembly of large macromolecular complexes. It is also involved in pathways like Fanconi Anemia, nonsense-mediated mRNA decay, and has connections to various diseases [1].

In colorectal cancer, loss of Ruvbl1/2 preferentially impairs the growth of YTHDF1-high cancer cells, patient-derived organoids, and xenografts, as they form a positive feedforward circuit with YTHDF1 to accelerate oncogenic translation [2]. In breast cancer, Ruvbl1 ubiquitination by DTL promotes Ruvbl1/2-β-catenin-mediated transcriptional regulation of the NHEJ pathway, enhancing radiation resistance [3]. In pancreatic cancer, degradation of Ruvbl1 leads to the arrest of cancer cells and tumor regression in mice, identifying it as a druggable vulnerability in MYC-driven cancer [4]. In tongue squamous cell carcinoma, overexpressing Ruvbl1 enhances cell viability, invasion, and drug resistance via the CRaf/MEK/ERK pathway [5]. In prostate tumors, Ruvbl1 promotes enzalutamide resistance through the PLXNA1-CRAF-MAPK pathway [6].

In conclusion, Ruvbl1 is a crucial protein involved in multiple cellular functions and disease-related pathways. Studies using gene-knockout or conditional-knockout models in mice and other loss-of-function experiments have revealed its role in various diseases, including colorectal, breast, pancreatic, tongue squamous cell, and prostate cancers. These findings highlight its potential as a therapeutic target for treating these malignancies.