MELK
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 expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.[9]
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.[10][11][12][13]
Interactions
MELK has been shown to interact with CDC25B.[14]
gollark: Time... isn't random, though.
gollark: According to the internet, RDRAND uses some sort of "hardware entropy source" (electrical noise?) fed into something something AES fed into a PRNG.
gollark: > or read the CMOS memory using inb/outbIsn't that the memory storing the BIOS and its data? Why is that random?
gollark: Clearly, things weren't random enough when you tried.
gollark: I ran it through valgrind, but that just complains about the standard library doing evil things in some other bits of the code, and seems to suggest mine is fine.
References
- GRCh38: Ensembl release 89: ENSG00000165304 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000035683 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 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.
- 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.
- "Entrez Gene: MELK maternal embryonic leucine zipper kinase".
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T (2007). "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 Research. 9 (1): R17. doi:10.1186/bcr1650. PMC 1851384. PMID 17280616.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- Beullens M, Vancauwenbergh S, Morrice N, Derua R, Ceulemans H, Waelkens E, Bollen M (December 2005). "Substrate specificity and activity regulation of protein kinase MELK". The Journal of Biological Chemistry. 280 (48): 40003–11. doi:10.1074/jbc.M507274200. PMID 16216881.
- Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, et al. (March 2004). "Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1". The Journal of Biological Chemistry. 279 (10): 8642–7. doi:10.1074/jbc.M311466200. PMID 14699119.
- 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.
- Seong HA, Gil M, Kim KT, Kim SJ, Ha H (February 2002). "Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38)". The Biochemical Journal. 361 (Pt 3): 597–604. doi:10.1042/0264-6021:3610597. PMC 1222342. PMID 11802789.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Gil M, Yang Y, Lee Y, Choi I, Ha H (August 1997). "Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells". Gene. 195 (2): 295–301. doi:10.1016/S0378-1119(97)00181-9. PMID 9305775.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
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