Download Gene Section MELK (maternal embryonic leucine zipper kinase) in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Short Communication
MELK (maternal embryonic leucine zipper kinase)
Jean-Pierre Tassan
CNRS UMR 6061 Universite de Rennes 1, IFR140 GFAS, Faculte de medecine, 2 avenue du Professeur
Leon Bernard, CS 34317, 35043 Rennes Cedex, France (JPT)
Published in Atlas Database: November 2011
Online updated version : http://AtlasGeneticsOncology.org/Genes/MELKID43360ch9p13.html
DOI: 10.4267/2042/47299
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
undetectable in cells which have exited cell cycle
(Badouel et al., 2010).
Other names: HPK38, KIAA0175, pEg3 kinase
HGNC (Hugo): MELK
Location: 9p13.2
Localisation
DNA/RNA
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).
Cytoplasm, nucleus and cell cortex.
Function
Description
The gene encompasses 105 kb; it has 18 exons.
Transcription
The MELK gene generates multiple variants
(potentially 28 different mRNAs). The longest mRNA
is composed of 3218 nucleotides.
Protein
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.
Homology
Description
Various cancers
The full-length protein is 651 amino acids with an
estimated molecular weight of approximately 74,5 kDa.
Note
Expression of MELK is more elevated in multiple
cancers including colon, lung and ovary relative to
corresponding normal tissues. Elevated MELK
expression is correlated with cell transformation (Gray
et al., 2005).
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.
Implicated in
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 germcell 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
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
Brain tumors
Note
Expression of MELK was significantly higher in highly
invasive glioblastomas multiform compared to benign
273
MELK (maternal embryonic leucine zipper kinase)
Tassan JP
Jung H, Seong HA, Ha H. Murine protein serine/threonine
kinase 38 activates apoptosis signal-regulating kinase 1 via
Thr 838 phosphorylation. J Biol Chem. 2008 Dec
12;283(50):34541-53
pilocytic astrocytomas (Marie et al., 2008).
Prognosis
Elevated MELK expression is associated with more
aggressive behaviour and associated with poor
prognosis of glioblastomas patients (Marie et al., 2008;
Nakano et al., 2008).
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.
Maternal embryonic leucine zipper kinase transcript
abundance correlates with malignancy grade in human
astrocytomas. Int J Cancer. 2008 Feb 15;122(4):807-15
Breast cancer
Note
MELK expression was found significantly upregulated
in the breast cancers (Pickard et al., 2009).
Prognosis
MELK expression is associated with poor patient
survival.
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. Maternal
embryonic leucine zipper kinase is a key regulator of the
proliferation of malignant brain tumors, including brain tumor
stem cells. J Neurosci Res. 2008 Jan;86(1):48-60
References
Pickard MR, Green AR, Ellis IO, Caldas C, Hedge VL,
Mourtada-Maarabouni M, Williams GT. Dysregulated
expression of Fau and MELK is associated with poor prognosis
in breast cancer. Breast Cancer Res. 2009;11(4):R60
Blot J, Chartrain I, Roghi C, Philippe M, Tassan JP. Cell cycle
regulation of pEg3, a new Xenopus protein kinase of the
KIN1/PAR-1/MARK family. Dev Biol. 2002 Jan 15;241(2):32738
Badouel C, Chartrain I, Blot J, Tassan JP. Maternal embryonic
leucine zipper kinase is stabilized in mitosis by phosphorylation
and is partially degraded upon mitotic exit. Exp Cell Res. 2010
Aug 1;316(13):2166-73
Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A,
Rider MH, Stalmans W, Bollen M. Inhibition of spliceosome
assembly by the cell cycle-regulated protein kinase MELK and
involvement of splicing factor NIPP1. J Biol Chem. 2004 Mar
5;279(10):8642-7
Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J,
Oshima RG, Terskikh AV. Maternal embryonic leucine zipper
kinase is upregulated and required in mammary tumor-initiating
cells in vivo. Cancer Res. 2010 Nov 1;70(21):8863-73
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.
Maternal embryonic leucine zipper kinase/murine protein
serine-threonine kinase 38 is a promising therapeutic target for
multiple cancers. Cancer Res. 2005 Nov 1;65(21):9751-61
Le Page Y, Chartrain I, Badouel C, Tassan JP. A functional
analysis of MELK in cell division reveals a transition in the
mode of cytokinesis during Xenopus development. J Cell Sci.
2011 Mar 15;124(Pt 6):958-68
Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T.
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. Breast
Cancer Res. 2007;9(1):R17
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
This article should be referenced as such:
Tassan JP. MELK (maternal embryonic leucine zipper kinase).
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4):273-274.
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