Cytoplasmic dynein 1 (DYNC1)

Cytoplasmic dynein 1 is a massive, multi-subunit molecular motor complex that serves as the primary engine for minus-end-directed transport along microtubules in eukaryotic cells [6, 10]. It is responsible for the retrograde movement of various intracellular cargoes, including organelles like the Golgi apparatus and lysosomes, endosomes, and signaling complexes, particularly within the elongated axons of neurons [11, 16]. Beyond its transport roles, dynein 1 is essential for proper cell division, where it facilitates mitotic spindle positioning and chromosome segregation [5, 9]. Mutations in the dynein heavy chain (DYNC1H1) or its regulatory cofactors, such as dynactin and LIS1, are linked to a spectrum of 'dyneinopathies,' including spinal muscular atrophy, Charcot-Marie-Tooth disease, and malformations of cortical development [11, 13]. In the context of drug development, dynein is explored as a target in oncology for disrupting mitosis and Hedgehog signaling, as well as in virology for blocking the entry of viruses like HIV-1 and adenovirus that hijack the motor for nuclear transport [3, 9]. However, because dynein is vital for the survival and function of nearly all cell types, achieving therapeutic selectivity without significant systemic toxicity remains a major pharmacological challenge [1, 10].

Other names

Cytoplasmic dynein 1 heavy chain 1DYNC1H1DHC1MAP1CDynein heavy chain 1, cytoplasmic

Inhibition of the AAA+ ATPase motor domain to prevent ATP hydrolysis or decoupling of nucleotide turnover from microtubule binding, thereby blocking minus-end-directed movement.