Midasin AAA ATPase 1 (MDN1) (MDN1)

Midasin (MDN1) is a massive, highly conserved AAA+ ATPase (approximately 600 kDa) that serves as a critical nuclear chaperone in the biogenesis of the eukaryotic 60S ribosomal subunit (UniProt, NIH). It functions by utilizing the energy of ATP hydrolysis to mechanically remove assembly factors, such as the PeBoW and PELP1 complexes, from pre-ribosomal particles, thereby facilitating their maturation and subsequent export from the nucleus to the cytoplasm (UniProt, NIH). Structurally, Midasin is characterized by a hexameric AAA+ ring and a long flexible tail ending in a Metal Ion-Dependent Adhesion Site (MIDAS) domain, which mediates substrate binding (NIH). In human health, MDN1 has been identified as a susceptibility gene for epilepsy and its mutations are associated with poor prognosis and high tumor mutation burden in breast cancer (NIH). Due to its essential role in cell growth and proliferation, Midasin is emerging as a potential therapeutic target, with small-molecule inhibitors like ribozinoindoles being developed to disrupt ribosome assembly in cancer cells (Patsnap, NIH).

Other names

MidasinRea1KIAA0301Dynein-related AAA-ATPase MDN1MIDAS-containing protein

Inhibition of MDN1 ATPase activity, which prevents the mechanical removal of assembly factors from pre-60S ribosomal subunits, thereby arresting ribosome maturation and nuclear export.