Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy

Abstract

The human genome encodes more than 500 protein kinases that work by transferring the γ-phosphate group from ATP to serine, threonine, or tyrosine (Ser/Thr/Tyr) residues. Various kinases are associated with the onset of cancer and its further progression. The recent advancements in developing small-molecule kinase inhibitors to treat different cancer types have shown noticeable results in clinical therapies. Microtubule-affinity regulating kinase 4 (MARK-4) is a Ser/Thr protein kinase that relates structurally to AMPK/Snf1 subfamily of the CaMK kinases. The protein kinase modulates major signalling pathways such as NF-κB, mTOR and the Hippo-signalling pathway. MARK4 is associated with various cancer types due to its important role in regulating microtubule dynamics and subsequent cell division. Aberrant expression of MARK4 is linked with several pathologies such as cancer, Alzheimer's disease, obesity, etc. This review provides detailed information on structural aspects of MARK4 and its role in various signalling pathways related to cancer. Several therapeutic molecules were designed to inhibit the MARK4 activity from controlling associated diseases. The review further highlights kinase-targeted drug discovery and development in oncology and cancer therapies. Finally, we summarize the latest findings regarding the role of MARK4 in cancer, diabetes, and neurodegenerative disease path to provide a solid rationale for future investigation and therapeutic intervention.