Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation

Abstract

Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)–positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain.

Maternal Embryonic Leucine Zipper Kinase (MELK) Reduces Replication Stress in Glioblastoma Cells

“…MELK has also been suggested to contribute to cell cycle progression, but, remarkably, both the knockdown and overexpression of MELK were reported to cause a G 2 /M arrest (20). Other data are indicative for a role of MELK in G 1 /S transition (8).…”

Cortical localization of Maternal Embryonic Leucine zipper Kinase (MELK) implicated in cytokinesis in early Xenopus embryos

“…MELK was shown to be involved in the control of cell proliferation, 3,4 regulation of apoptosis, 5 inhibition of spliceosome assembly, 6 haematopoiesis, 7 asymmetric cell divisions 8 and cell cycle. of biological processes, its precise function remains elusive.…”

Analysis of stemness gene expression and CD133 abnormal methylation in neuroblastoma cell lines

“…MELK1 knockdown by siRNA resulted in reducing the survival and producing the depletion of stem cells isolated from GB in vitro (26). The implication of this gene in neuroblastoma biology has not been described, but there is increasing evidence that it is required for NSC selfrenewal (27).…”