MELK

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MELK
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMELK, HPK38, maternal embryonic leucine zipper kinase
External IDsOMIM: 607025 MGI: 106924 HomoloGene: 32111 GeneCards: MELK
EC number2.7.10.2
Gene location (Human)
Chromosome 9 (human)
Chr.Chromosome 9 (human)[1]
Chromosome 9 (human)
Genomic location for MELK
Genomic location for MELK
Band9p13.2Start36,572,862 bp[1]
End36,677,683 bp[1]
RNA expression pattern
PBB GE MELK 204825 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_010790

RefSeq (protein)

NP_034920

Location (UCSC)Chr 9: 36.57 – 36.68 MbChr 4: 44.3 – 44.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Maternal embryonic leucine zipper kinase (MELK) is an enzyme that in humans is encoded by the MELK gene.[5][6][7] MELK is a serine/threonine kinase belonging to the family of AMPK/snf1 protein kinases. MELK was first identified present as maternal mRNA in mouse embryos.[8] MELK has been shown to involved in progression through the cell cycle, possibly linked to its interaction with CDC25B.[9]

MELK expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.[10] MELK was previously believed to be essential for cancer cell proliferation. However, recent research using CRISPR has demonstrated that MELK is fully dispensable for cancer cell growth, casting doubt on the rationale for targeting this protein in patients.[11][12][13][14]

Interactions[edit]

MELK has been shown to interact with CDC25B.[15]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000165304 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035683 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (February 1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849.
  6. ^ Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL (June 1997). "New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo". Molecular Reproduction and Development. 47 (2): 148–56. doi:10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M. PMID 9136115.
  7. ^ "Entrez Gene: MELK maternal embryonic leucine zipper kinase".
  8. ^ Heyer BS, Kochanowski H, Solter D (August 1999). "Expression of Melk, a new protein kinase, during early mouse development". Developmental Dynamics. 215 (4): 344–51. doi:10.1002/(SICI)1097-0177(199908)215:4<344::AID-AJA6>3.0.CO;2-H. PMID 10417823.
  9. ^ Nakano I, Paucar AA, Bajpai R, Dougherty JD, Zewail A, Kelly TK, et al. (August 2005). "Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation". The Journal of Cell Biology. 170 (3): 413–27. doi:10.1083/jcb.200412115. PMC 2171475. PMID 16061694.
  10. ^ Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, et al. (November 2005). "Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers". Cancer Research. 65 (21): 9751–61. doi:10.1158/0008-5472.CAN-04-4531. PMID 16266996.
  11. ^ Lin A, Giuliano CJ, Sayles NM, Sheltzer JM (March 2017). "CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials". eLife. 6. doi:10.7554/eLife.24179. PMID 28337968.
  12. ^ Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, et al. (September 2017). "MELK is not necessary for the proliferation of basal-like breast cancer cells". eLife. 6. doi:10.7554/eLife.26693. PMID 28926338.
  13. ^ Giuliano CJ, Lin A, Smith JC, Palladino AC, Sheltzer JM (February 2018). "MELK expression correlates with tumor mitotic activity but is not required for cancer growth". eLife. 7. doi:10.7554/eLife.32838. PMID 29417930.
  14. ^ Settleman J, Sawyers CL, Hunter T (February 2018). "Challenges in validating candidate therapeutic targets in cancer". eLife. 7. doi:10.7554/eLife.32402. PMID 29417929.
  15. ^ Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP (October 2002). "Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation". Oncogene. 21 (50): 7630–41. doi:10.1038/sj.onc.1205870. PMID 12400006.

Further reading[edit]