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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{PBB|geneid=9833}}
{{Infobox_gene}}
'''Maternal embryonic leucine zipper kinase''' is an [[enzyme]] that in humans is encoded by the ''MELK'' [[gene]].<ref name="pmid8724849">{{cite journal | author = Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N | title = 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 | journal = DNA Res | volume = 3 | issue = 1 | pages = 17–24 | year = 1996 | month = Nov | pmid = 8724849 | pmc = | doi = }}</ref><ref name="pmid9136115">{{cite journal | author = Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL | title = New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo | journal = Mol Reprod Dev | volume = 47 | issue = 2 | pages = 148–56 | year = 1997 | month = Aug | pmid = 9136115 | pmc = | doi = 10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MELK maternal embryonic leucine zipper kinase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9833| accessdate = }}</ref>
'''Maternal embryonic leucine zipper kinase (MELK)''' is an [[enzyme]] that in humans is encoded by the ''MELK'' [[gene]].<ref name="pmid8724849">{{cite journal | vauthors = Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N | title = 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 | journal = DNA Research | volume = 3 | issue = 1 | pages = 17–24 | date = February 1996 | pmid = 8724849 | doi = 10.1093/dnares/3.1.17 | doi-access = free }}</ref><ref name="pmid9136115">{{cite journal | vauthors = Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL | title = New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo | journal = Molecular Reproduction and Development | volume = 47 | issue = 2 | pages = 148–56 | date = June 1997 | pmid = 9136115 | doi = 10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M | s2cid = 27882565 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MELK maternal embryonic leucine zipper kinase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9833}}</ref> MELK is a [[Serine/threonine-specific protein kinase|serine/threonine kinase]] belonging to the family of AMPK/Snf1 protein kinases. MELK was first identified present as maternal mRNA in mouse embryos.<ref>{{cite journal | vauthors = Heyer BS, Kochanowski H, Solter D | title = Expression of Melk, a new protein kinase, during early mouse development | journal = Developmental Dynamics | volume = 215 | issue = 4 | pages = 344–51 | date = August 1999 | pmid = 10417823 | doi = 10.1002/(SICI)1097-0177(199908)215:4<344::AID-AJA6>3.0.CO;2-H | doi-access = free }}</ref> MELK expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers | journal = Cancer Research | volume = 65 | issue = 21 | pages = 9751–61 | date = November 2005 | pmid = 16266996 | doi = 10.1158/0008-5472.CAN-04-4531 | doi-access = free }}</ref>


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. <ref>{{cite journal | vauthors = Lin A, Giuliano CJ, Sayles NM, Sheltzer JM | title = CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials | journal = eLife | volume = 6 | date = March 2017 | pmid = 28337968 | doi = 10.7554/eLife.24179 | pmc = 5365317 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, Buckley DL, Nabet B, Roberts JM, Paulk J, Dastjerdi S, Winter GE, McLauchlan H, Moran J, Bradner JE, Eck MJ, Dhe-Paganon S, Zhao JJ, Gray NS | display-authors = 6 | title = MELK is not necessary for the proliferation of basal-like breast cancer cells | journal = eLife | volume = 6 | date = September 2017 | pmid = 28926338 | doi = 10.7554/eLife.26693 | pmc = 5605198 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Giuliano CJ, Lin A, Smith JC, Palladino AC, Sheltzer JM | title = MELK expression correlates with tumor mitotic activity but is not required for cancer growth | journal = eLife | volume = 7 | date = February 2018 | pmid = 29417930 | doi = 10.7554/eLife.32838 | pmc = 5805410 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Settleman J, Sawyers CL, Hunter T | title = Challenges in validating candidate therapeutic targets in cancer | journal = eLife | volume = 7 | date = February 2018 | pmid = 29417929 | doi = 10.7554/eLife.32402 | pmc = 5805407 | doi-access = free }}</ref>
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==Interactions==
== Interactions ==
⚫
MELK has been shown to [[Protein-protein_interaction|interact]] with [[CDC25B]].<ref name=pmid12400006>{{cite journal | quotes = yes |last=Davezac |first=Noélie |authorlink= |coauthors=Baldin Véronique, Blot Joëlle, Ducommun Bernard, Tassan Jean-Pierre |year=[[2002]]|month=Oct. |title=Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation |journal=Oncogene |volume=21 |issue=50 |pages=7630–41 |publisher= |location = England| issn = 0950-9232| pmid = 12400006 |doi = 10.1038/sj.onc.1205870 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>


⚫
MELK has been shown to [[Protein-protein interaction|interact]] with [[CDC25B]].<ref name=pmid12400006>{{cite journal | vauthors = Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP | title = Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation | journal = Oncogene | volume = 21 | issue = 50 | pages = 7630–41 | date = October 2002 | pmid = 12400006 | doi = 10.1038/sj.onc.1205870 | doi-access = free }}</ref>
⚫
==References==

⚫
== References ==
{{reflist}}
{{reflist}}

==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T | title = 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 | journal = Breast Cancer Research | volume = 9 | issue = 1 | pages = R17 | year = 2007 | pmid = 17280616 | pmc = 1851384 | doi = 10.1186/bcr1650 | doi-access = free }}
{{PBB_Further_reading
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
| citations =
*{{cite journal | author=Lin ML, Park JH, Nishidate T, ''et al.'' |title=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. |journal=Breast Cancer Res. |volume=9 |issue= 1 |pages= R17 |year= 2007 |pmid= 17280616 |doi= 10.1186/bcr1650 }}
* {{cite journal | vauthors = Beullens M, Vancauwenbergh S, Morrice N, Derua R, Ceulemans H, Waelkens E, Bollen M | title = Substrate specificity and activity regulation of protein kinase MELK | journal = The Journal of Biological Chemistry | volume = 280 | issue = 48 | pages = 40003–11 | date = December 2005 | pmid = 16216881 | doi = 10.1074/jbc.M507274200 | doi-access = free }}
*{{cite journal | author=Olsen JV, Blagoev B, Gnad F, ''et al.'' |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 }}
* {{cite journal | vauthors = Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, Stalmans W, Bollen M | display-authors = 6 | title = Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 10 | pages = 8642–7 | date = March 2004 | pmid = 14699119 | doi = 10.1074/jbc.M311466200 | doi-access = free }}
*{{cite journal | author=Beullens M, Vancauwenbergh S, Morrice N, ''et al.'' |title=Substrate specificity and activity regulation of protein kinase MELK. |journal=J. Biol. Chem. |volume=280 |issue= 48 |pages= 40003–11 |year= 2006 |pmid= 16216881 |doi= 10.1074/jbc.M507274200 }}
* {{cite journal | vauthors = Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP | title = Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation | journal = Oncogene | volume = 21 | issue = 50 | pages = 7630–41 | date = October 2002 | pmid = 12400006 | doi = 10.1038/sj.onc.1205870 | doi-access = free }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Seong HA, Gil M, Kim KT, Kim SJ, Ha H | title = Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38) | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 597–604 | date = February 2002 | pmid = 11802789 | pmc = 1222342 | doi = 10.1042/0264-6021:3610597 }}
*{{cite journal | author=Vulsteke V, Beullens M, Boudrez A, ''et al.'' |title=Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1. |journal=J. Biol. Chem. |volume=279 |issue= 10 |pages= 8642–7 |year= 2004 |pmid= 14699119 |doi= 10.1074/jbc.M311466200 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Gil M, Yang Y, Lee Y, Choi I, Ha H | title = Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells | journal = Gene | volume = 195 | issue = 2 | pages = 295–301 | date = August 1997 | pmid = 9305775 | doi = 10.1016/S0378-1119(97)00181-9 }}
*{{cite journal | author=Davezac N, Baldin V, Blot J, ''et al.'' |title=Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation. |journal=Oncogene |volume=21 |issue= 50 |pages= 7630–41 |year= 2002 |pmid= 12400006 |doi= 10.1038/sj.onc.1205870 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Seong HA, Gil M, Kim KT, ''et al.'' |title=Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38). |journal=Biochem. J. |volume=361 |issue= Pt 3 |pages= 597–604 |year= 2002 |pmid= 11802789 |doi=10.1042/0264-6021:3610597 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Gil M, Yang Y, Lee Y, ''et al.'' |title=Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells. |journal=Gene |volume=195 |issue= 2 |pages= 295–301 |year= 1997 |pmid= 9305775 |doi=10.1016/S0378-1119(97)00181-9 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
}}
{{refend}}
{{refend}}


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{{gene-9-stub}}
{{Serine/threonine-specific protein kinases}}
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}


[[Category:EC 2.7.11]]
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Latest revision as of 02:25, 3 December 2023

MELK
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMELK, HPK38, maternal embryonic leucine zipper kinase
External IDsOMIM: 607025; MGI: 106924; HomoloGene: 32111; GeneCards: MELK; OMA:MELK - orthologs
EC number2.7.10.2
Orthologs
SpeciesHumanMouse
Entrez

9833

17279

Ensembl

ENSG00000165304

ENSMUSG00000035683

UniProt

Q14680

Q61846

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 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. The results are dependent on the experimental design. Therefore, there is a need for further research. [10][11][12][13]

Interactions

[edit]

MELK has been shown to interact with CDC25B.[14]

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. S2CID 27882565.
  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. ^ 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.
  10. ^ 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. PMC 5365317. PMID 28337968.
  11. ^ 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. PMC 5605198. PMID 28926338.
  12. ^ 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. PMC 5805410. PMID 29417930.
  13. ^ Settleman J, Sawyers CL, Hunter T (February 2018). "Challenges in validating candidate therapeutic targets in cancer". eLife. 7. doi:10.7554/eLife.32402. PMC 5805407. PMID 29417929.
  14. ^ 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]


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