Cell-cycle dependent localization of MELK and its new partner RACK1 in epithelial versus mesenchyme-like cells in Xenopus embryo

Abstract

SummaryMaternal Embryonic Leucine zipper Kinase (MELK) was recently shown to be involved in cell division of Xenopus embryo epithelial cells. The cytokinetic furrow of these cells ingresses asymmetrically and is developmentally regulated. Two subpopulations of xMELK, the mMELK (for “mitotic” xMELK) and iMELK (“interphase” xMELK), which differ in their spatial and temporal regulation, are detected in Xenopus embryo. How cells regulate these two xMELK populations is unknown. In this study we show that, in epithelial cells, xMELK is present at a higher concentration at the apical junctional complex, in contrast to mesenchyme-like cells, which have uniform distribution of cortical MELK. Interestingly, mMELK and iMELK also differ by their requirements towards cell–cell contacts to establish their proper cortical localization both in epithelial and mesenchyme-like cells. Receptor for Activated protein Kinase C (RACK1), which we identified as an xMELK partner, co-localizes with xMELK at the tight junction. Moreover, a truncated RACK1 construct interferes with iMELK localization at cell–cell contacts. Collectively, our results suggest that iMELK and RACK1 are present in the same complex and that RACK1 is involved in the specific recruitment of iMELK at the apical junctional complex in epithelial cells of Xenopus embryos.

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers

“…2006 ), we first monitored MELK-GFP localization throughout the cell cycle by time-lapse imaging. We found, in agreement with other studies ( Chartrain et al 2006 , 2013 ; Tipton et al 2012 ), that MELK localizes to the mitotic cleavage furrow during cytokinesis in RPE1 cells ( Figure 2C ). We therefore next introduced the live-cell nuclear stain SiR-DNA (Spirochrome) into doxycycline-inducible MELK-GFP RPE1 cells to label the chromatin and used time-lapse imaging microscopy to investigate the effect of MELK-GFP overexpression in mitosis.…”

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers

“…As MELK was previously shown to be involved in cytokinesis in Xenopus embryos [20] and mammalian cells [21], we first monitored MELK-GFP localization throughout the cell cycle by time-lapse imaging. We found, in agreement with other studies [39][40][41], that MELK localizes to the mitotic cleavage furrow during cytokinesis in RPE1 cells (Fig. 2C).…”

MELK is an oncogenic kinase essential for metastasis, mitotic progression, and programmed death in lung carcinoma

“… 5 Numerous studies have demonstrated that MELK is a cell-cycle modulator essential for mitotic progression. 6 , 7 Moreover, MELK also participates in other important processes, such as stem cell self-renewal, 8 , 9 and apoptosis inhibition. 10 , 11 Furthermore, MELK is overexpressed in various cancers and high expression of MELK is related with poor prognosis.…”