Nuclear valosin-containing protein-like (NVL)

Nuclear valosin-containing protein-like (NVL) is a member of the AAA+ (ATPases Associated with diverse cellular Activities) family that functions as a hexameric molecular machine essential for ribosome biogenesis (1.1.1, 1.2.4). Specifically, NVL acts as a protein unfoldase that uses the energy of ATP hydrolysis to remodel pre-ribosomal particles and release assembly factors, thereby driving the maturation of the large (60S) ribosomal subunit (1.3.1, 1.3.2). In the context of oncology, cancer cells exhibit a high demand for ribosome production to sustain rapid proliferation, making NVL a significant therapeutic vulnerability (1.3.3, 1.3.4). Recent drug development efforts have identified small-molecule inhibitors like MM17 and its bioavailable analog MM927, which selectively target NVL to induce p53-mediated apoptosis in various cancer models, including leukemia and colorectal cancer (1.2.3, 1.3.2). Beyond its role in cancer, NVL is recognized as a novel autoantigen in systemic sclerosis, where the presence of anti-NVL autoantibodies is associated with specific clinical phenotypes such as calcinosis and an increased risk of synchronous malignancy (1.4.2, 1.4.5).

Other names

NVLpNVL2Nuclear VCP-like proteinNuclear valosin-containing protein-like protein

Direct inhibition of the NVL ATPase activity arrests the maturation of the 60S ribosomal subunit in the nucleolus, which triggers the nucleolar stress response, stabilizes p53 via MDM2 inhibition, and induces cell cycle arrest or apoptosis (1.2.2, 1.3.2).