MELK

MELK Full Name

maternal embryonic leucine zipper kinase

MELK Introduction

Maternal embryonic leucine zipper kinase (MELK) is a serine/threonine kinase of the AMPK-related family that is highly expressed in proliferating cells and in many cancers. The protein contains an N-terminal kinase domain, a central ubiquitin-associated (UBA) domain, and a C-terminal KA1 domain that mediates membrane association and autoinhibition. MELK is enriched in stem and progenitor populations, where it supports cell-cycle progression and survival under stress. The human gene maps to chromosome 9p13.2 and is amplified or overexpressed in multiple malignancies.

Figure 1. The structure of MELK.

Cell-Cycle Regulation and Stress Adaptation
MELK phosphorylates a wide range of substrates including CDC25B, PDCD4, eIF2B, and Bcl-G, modulating cell-cycle progression, translation initiation, and apoptosis. MELK activity peaks during mitosis, where it supports proper spindle assembly and chromosome segregation, and it is also upregulated during the G2/M DNA-damage checkpoint. Through its UBA domain, MELK binds ubiquitin and may participate in substrate recruitment to the proteasome, and through the KA1 domain it localizes to membrane compartments where it can respond to stress-induced changes in lipid signaling.

Cancer Stem Cells and Therapeutic Targeting
MELK is overexpressed in triple-negative breast cancer, glioblastoma, and acute myeloid leukemia, where its expression correlates with cancer stem cell frequency, treatment resistance, and poor prognosis. The small-molecule MELK inhibitor OTSSP167 has shown preclinical efficacy in tumor xenograft models, although recent reports suggest that some of its effects may stem from off-target cytotoxicity. Nevertheless, MELK remains an active target for antibody-drug conjugates and PROTAC-based degraders, with multiple programs in early-phase trials for MELK-high solid tumors.

Alternate Names for MELK

MELK; maternal embryonic leucine zipper kinase; HPK38; pEg3 kinase; protein kinase Eg3; protein kinase PK38; tyrosine-protein kinase MELK;