Biology:MELK

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Maternal embryonic leucine zipper kinase (MELK) is an enzyme that in humans is encoded by the MELK gene.[1][2][3] 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.[4] MELK expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.[5]

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. The results are dependent on the experimental design. Therefore, there is a need for further research. [6][7][8][9]

Interactions

MELK has been shown to interact with CDC25B.[10]

References

  1. "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. February 1996. doi:10.1093/dnares/3.1.17. PMID 8724849. 
  2. "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. June 1997. doi:10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M. PMID 9136115. 
  3. "Entrez Gene: MELK maternal embryonic leucine zipper kinase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9833. 
  4. "Expression of Melk, a new protein kinase, during early mouse development". Developmental Dynamics 215 (4): 344–51. August 1999. doi:10.1002/(SICI)1097-0177(199908)215:4<344::AID-AJA6>3.0.CO;2-H. PMID 10417823. 
  5. "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. November 2005. doi:10.1158/0008-5472.CAN-04-4531. PMID 16266996. 
  6. "CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials". eLife 6. March 2017. doi:10.7554/eLife.24179. PMID 28337968. 
  7. "MELK is not necessary for the proliferation of basal-like breast cancer cells". eLife 6. September 2017. doi:10.7554/eLife.26693. PMID 28926338. 
  8. "MELK expression correlates with tumor mitotic activity but is not required for cancer growth". eLife 7. February 2018. doi:10.7554/eLife.32838. PMID 29417930. 
  9. "Challenges in validating candidate therapeutic targets in cancer". eLife 7. February 2018. doi:10.7554/eLife.32402. PMID 29417929. 
  10. "Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation". Oncogene 21 (50): 7630–41. October 2002. doi:10.1038/sj.onc.1205870. PMID 12400006. 

Further reading