Microtubule affinity regulating kinase 1 (MARK1) (MARK1)

Microtubule affinity regulating kinase 1 (MARK1) is a serine/threonine-protein kinase belonging to the CAMK family that plays a critical role in establishing cell polarity and regulating microtubule dynamics. It functions by phosphorylating microtubule-associated proteins (MAPs) such as Tau, MAP2, and MAP4 at specific KXGS motifs, which causes their detachment from microtubules and leads to microtubule disassembly. In the context of neurodegenerative disease, MARK1 is a key mediator of early Tau hyperphosphorylation (specifically at Ser262), a process that precedes the formation of neurofibrillary tangles in Alzheimer's disease. Beyond its role in the central nervous system, MARK1 is implicated in various cancers, including hepatocellular carcinoma and colorectal cancer, where it regulates malignant progression and sensitivity to therapeutic agents like sorafenib. As a therapeutic target, MARK1 is being explored for the development of small-molecule inhibitors aimed at stabilizing the cytoskeleton in neurodegeneration and modulating oncogenic signaling in oncology.

Other names

MARKPAR-1CSerine/threonine-protein kinase MARK1KIAA1477Par1cMAP/microtubule affinity-regulating kinase 1PAR1 homolog c

Inhibition of MARK1 prevents the phosphorylation of microtubule-associated proteins (MAPs) such as Tau, thereby stabilizing microtubules and potentially reducing the formation of neurofibrillary tangles in neurodegenerative diseases. In oncology, MARK1 modulation affects cell proliferation and drug resistance, such as enhancing sorafenib sensitivity in hepatocellular carcinoma.