MELK (maternal embryonic leucine zipper kinase)

2011-11-01   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

Identity

HGNC
LOCATION
9p13.2
LOCUSID
ALIAS
HPK38
FUSION GENES

DNA/RNA

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.

Proteins

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.

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.

Implicated in

Entity name
Various cancers
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).
Entity name
Brain tumors
Note
Expression of MELK was significantly higher in highly invasive glioblastomas multiform compared to benign 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).
Entity name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
204208232010Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit.Badouel C et al
117841152002Cell cycle regulation of pEg3, a new Xenopus protein kinase of the KIN1/PAR-1/MARK family.Blot J et al
162669962005Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers.Gray D et al
208611862010Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo.Hebbard LW et al
189482612008Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation.Jung H et al
213783122011A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development.Le Page Y et al
172806162007Involvement 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 et al
179606222008Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas.Marie SK et al
177220612008Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.Nakano I et al
196711592009Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer.Pickard MR et al
146991192004Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1.Vulsteke V et al

Other Information

Locus ID:

NCBI: 9833
MIM: 607025
HGNC: 16870
Ensembl: ENSG00000165304

Variants:

dbSNP: 9833
ClinVar: 9833
TCGA: ENSG00000165304
COSMIC: MELK

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000165304ENST00000298048Q14680
ENSG00000165304ENST00000495529A0A0D9SGI4
ENSG00000165304ENST00000536329Q14680
ENSG00000165304ENST00000536860Q14680
ENSG00000165304ENST00000536987Q14680
ENSG00000165304ENST00000541717Q14680
ENSG00000165304ENST00000543751Q14680
ENSG00000165304ENST00000545008Q14680
ENSG00000165304ENST00000625974A0A0D9SFL8
ENSG00000165304ENST00000626154A0A0D9SFF9
ENSG00000165304ENST00000627766A0A0D9SFB9

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
177220612008Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.78
172806162007Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family.71
256012062015EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner.67
232833052012Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer.65
179606222008Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas.64
196711592009Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer.63
162168812005Substrate specificity and activity regulation of protein kinase MELK.46
248442442014MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells.46
229452372013The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer.45
124000062002Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation.37

Citation

Jean-Pierre Tassan

MELK (maternal embryonic leucine zipper kinase)

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/gene/43360/melk