| Note | MELK (Maternal Embryonic Leucine zipper Kinase) belongs to the CAMK serine/threonine protein kinase superfamily. Melk is a protein serine/threonine kinase that is maximally active during mitosis. It is involved in diverse functions such as cell cycle, cytokinesis, mRNA splicing and apoptosis. |
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| Description | The full-length protein is 651 amino acids with an estimated molecular weight of approximately 74,5 kDa. |
| Expression | MELK is expressed in cells of various tissue origins. MELK is highly expressed in oocytes, spermatogonia and embryos, which is indicative of a role in the germ-cell development. MELK is highly expressed in a large panel of cancers MELK expression is dependant on cell transformation (Gray et al., 2005). Its expression is strongly dependant on cell-cycle: MELK is undetectable in cells which have exited cell cycle (Badouel et al., 2010). |
| Localisation | Cytoplasm, nucleus and cell cortex. |
| Function | The exact function of MELK is currently unknown, however MELK was shown to be involved in cell cycle progression via the protein phosphatase CDC25B phosphorylation (Blot et al., 2002), in cytokinesis (Le Page et al., 2011), in apoptosis via its interaction with the Bcl-2 family of proapoptotic genes (Lin et al., 2007) and apoptosis signal-regulating kinase (ASK1) (Jung et al., 2008) and in inhibition of mRNA splicing during mitosis via its association with NIPP1 (Vulsteke et al., 2004). MELK function is required for mammary tumorigenesis in vivo (Hebbard et al., 2010). |
| Homology | MELK belongs to the Kin1/PAR-1/MARK family of protein kinases found from yeast to human. These kinases are involved in cell polarity, dynamics of microtubules and intracellular signalisation. |
| Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit. |
| Badouel C, Chartrain I, Blot J, Tassan JP. |
| Exp Cell Res. 2010 Aug 1;316(13):2166-73. Epub 2010 Apr 24. |
| PMID 20420823 |
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| Cell cycle regulation of pEg3, a new Xenopus protein kinase of the KIN1/PAR-1/MARK family. |
| Blot J, Chartrain I, Roghi C, Philippe M, Tassan JP. |
| Dev Biol. 2002 Jan 15;241(2):327-38. |
| PMID 11784115 |
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| Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers. |
| Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP. |
| Cancer Res. 2005 Nov 1;65(21):9751-61. |
| PMID 16266996 |
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| Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo. |
| Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J, Oshima RG, Terskikh AV. |
| Cancer Res. 2010 Nov 1;70(21):8863-73. Epub 2010 Sep 22. |
| PMID 20861186 |
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| Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation. |
| Jung H, Seong HA, Ha H. |
| J Biol Chem. 2008 Dec 12;283(50):34541-53. Epub 2008 Oct 23. |
| PMID 18948261 |
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| A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development. |
| Le Page Y, Chartrain I, Badouel C, Tassan JP. |
| J Cell Sci. 2011 Mar 15;124(Pt 6):958-68. |
| PMID 21378312 |
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| Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. |
| Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T. |
| Breast Cancer Res. 2007;9(1):R17. |
| PMID 17280616 |
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| Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas. |
| Marie SK, Okamoto OK, Uno M, Hasegawa AP, Oba-Shinjo SM, Cohen T, Camargo AA, Kosoy A, Carlotti CG Jr, Toledo S, Moreira-Filho CA, Zago MA, Simpson AJ, Caballero OL. |
| Int J Cancer. 2008 Feb 15;122(4):807-15. |
| PMID 17960622 |
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| Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. |
| Nakano I, Masterman-Smith M, Saigusa K, Paucar AA, Horvath S, Shoemaker L, Watanabe M, Negro A, Bajpai R, Howes A, Lelievre V, Waschek JA, Lazareff JA, Freije WA, Liau LM, Gilbertson RJ, Cloughesy TF, Geschwind DH, Nelson SF, Mischel PS, Terskikh AV, Kornblum HI. |
| J Neurosci Res. 2008 Jan;86(1):48-60. |
| PMID 17722061 |
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| Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer. |
| Pickard MR, Green AR, Ellis IO, Caldas C, Hedge VL, Mourtada-Maarabouni M, Williams GT. |
| Breast Cancer Res. 2009;11(4):R60. Epub 2009 Aug 11. |
| PMID 19671159 |
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| Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1. |
| Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, Stalmans W, Bollen M. |
| J Biol Chem. 2004 Mar 5;279(10):8642-7. Epub 2003 Dec 29. |
| PMID 14699119 |
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