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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{PBB|geneid=6789}}
{{Infobox_gene}}
'''Serine/threonine-protein kinase 4''' is an [[enzyme]] that in humans is encoded by the ''STK4'' [[gene]].<ref name="pmid8816758">{{cite journal | author = Taylor LK, Wang HC, Erikson RL | title = Newly identified stress-responsive protein kinases, Krs-1 and Krs-2 | journal = Proc Natl Acad Sci U S A | volume = 93 | issue = 19 | pages = 10099–104 | date=November 1996| pmid = 8816758 | pmc = 38343 | doi =10.1073/pnas.93.19.10099 }}</ref><ref name="pmid9545236">{{cite journal | author = Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG | title = Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1 | journal = EMBO J | volume = 17 | issue = 8 | pages = 2224–34 | date=June 1998| pmid = 9545236 | pmc = 1170567 | doi = 10.1093/emboj/17.8.2224 }}</ref><ref name="pmid11517310">{{cite journal | author = Ura S, Masuyama N, Graves JD, Gotoh Y | title = Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation | journal = Proc Natl Acad Sci U S A | volume = 98 | issue = 18 | pages = 10148–53 | date=August 2001| pmid = 11517310 | pmc = 56930 | doi = 10.1073/pnas.181161698 }}</ref>
'''Serine/threonine-protein kinase 4''' is an [[enzyme]] that in humans is encoded by the ''STK4'' [[gene]].<ref name="pmid8816758">{{cite journal | vauthors = Taylor LK, Wang HC, Erikson RL | title = Newly identified stress-responsive protein kinases, Krs-1 and Krs-2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 19 | pages = 10099–104 | date = November 1996 | pmid = 8816758 | pmc = 38343 | doi = 10.1073/pnas.93.19.10099 | bibcode = 1996PNAS...9310099T | doi-access = free }}</ref><ref name="pmid9545236">{{cite journal | vauthors = Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG | title = Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1 | journal = EMBO J. | volume = 17 | issue = 8 | pages = 2224–34 | date = June 1998 | pmid = 9545236 | pmc = 1170567 | doi = 10.1093/emboj/17.8.2224 }}</ref><ref name="pmid11517310">{{cite journal | vauthors = Ura S, Masuyama N, Graves JD, Gotoh Y | title = Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 18 | pages = 10148–53 | date = August 2001 | pmid = 11517310 | pmc = 56930 | doi = 10.1073/pnas.181161698 | bibcode = 2001PNAS...9810148U | doi-access = free }}</ref>


== Function ==
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes [[autophosphorylation]]. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process.<ref name="entrez">{{cite web | title = Entrez Gene: STK4 serine/threonine kinase 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6789| accessdate = }}</ref>
}}


The protein encoded by this gene is a [[cytoplasmic]] kinase that is structurally similar to the yeast Ste20p (sterile 20 protein) kinase, which acts upstream of the stress-induced [[mitogen-activated protein kinase]] (MAPK) cascade. The encoded protein can [[phosphorylation|phosphorylate]] [[myelin]] basic protein and undergoes [[autophosphorylation]]. A [[caspase]]-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating [[histone H2B]]. The particular phosphorylation catalyzed by this protein has been correlated with [[apoptosis]], and it's possible that this protein induces the [[chromatin condensation]] observed in this process.<ref name="entrez">{{cite web | title = Entrez Gene: STK4 serine/threonine kinase 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6789}}</ref>
==Interactions==
STK4 has been shown to [[Protein-protein interaction|interact]] with [[PRKRIR]].<ref name=pmid12384512>{{cite journal |last=Lin |first=Yenshou |authorlink= |coauthors=Khokhlatchev Andrei, Figeys Daniel, Avruch Joseph |date=December 2002|title=Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis |journal=J. Biol. Chem. |volume=277 |issue=50 |pages=47991–8001 |publisher= |location = United States| issn = 0021-9258| pmid = 12384512 |doi = 10.1074/jbc.M202630200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>


==References==
== Interactions ==

STK4 has been shown to [[Protein-protein interaction|interact]] with [[PRKRIR]].<ref name=pmid12384512>{{cite journal | vauthors = Lin Y, Khokhlatchev A, Figeys D, Avruch J | title = Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis | journal = J. Biol. Chem. | volume = 277 | issue = 50 | pages = 47991–8001 | date = December 2002 | pmid = 12384512 | doi = 10.1074/jbc.M202630200 | doi-access = free }}</ref>

STK4 has also been shown to prevent, through Yap1 coactivator modulation, haematological tumor cell apoptosis.<ref>{{cite journal | vauthors = Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G | title = Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers | journal = Nat. Med. | volume = 20 | issue = 6 | pages = 599–606 | date = 2014 | pmid = 24813251 | doi = 10.1038/nm.3562 | pmc=4057660| url = https://dash.harvard.edu/bitstream/handle/1/13581189/4057660.pdf?sequence=1 }}</ref>

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


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
*{{cite journal | author=Juhyun Choi, ''et al.'' | editor1-last=Kaeberlein | editor1-first=Matt |title=Mst1-FoxO Signaling Protects Naïve T Lymphocytes from Cellular Oxidative Stress in Mice. |journal=PLoS one. |volume=4 |issue= 11 |pages= e8011 |year= 2009 |pmid= 19956688 |doi= 10.1371/journal.pone.0008011 | pmc=2776980}}
* {{cite journal | vauthors = Choi J, Oh S, Lee D, Oh HJ, Park JY, Lee SB, Lim DS | title = Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice | journal = PLOS ONE | volume = 4 | issue = 11 | pages = e8011 | year = 2009 | pmid = 19956688 | pmc = 2776980 | doi = 10.1371/journal.pone.0008011 | bibcode = 2009PLoSO...4.8011C | editor1-last = Kaeberlein | editor1-first = Matt | doi-access = free }}
* {{cite journal | vauthors = de Souza PM, Lindsay MA | title = Mammalian Sterile20-like kinase 1 and the regulation of apoptosis | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt3 | pages = 485–8 | year = 2004 | pmid = 15157167 | doi = 10.1042/BST0320485 }}
{{PBB_Further_reading
* {{cite journal | vauthors = Han S, Stuart LA, Degen SJ | title = Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor | journal = Biochemistry | volume = 30 | issue = 40 | pages = 9768–80 | year = 1991 | pmid = 1655021 | doi = 10.1021/bi00104a029 }}
| citations =
*{{cite journal | author=de Souza PM, Lindsay MA |title=Mammalian Sterile20-like kinase 1 and the regulation of apoptosis. |journal=Biochem. Soc. Trans. |volume=32 |issue= Pt3 |pages= 485–8 |year= 2005 |pmid= 15157167 |doi= 10.1042/BST0320485 }}
* {{cite journal | vauthors = Gerber MJ, Drabkin HA, Firnhaber C, Miller YE, Scoggin CH, Smith DI | title = Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel | journal = Am. J. Hum. Genet. | volume = 43 | issue = 4 | pages = 442–51 | year = 1988 | pmid = 2902784 | pmc = 1715492 }}
*{{cite journal | author=Han S, Stuart LA, Degen SJ |title=Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. |journal=Biochemistry |volume=30 |issue= 40 |pages= 9768–80 |year= 1991 |pmid= 1655021 |doi=10.1021/bi00104a029 }}
* {{cite journal | vauthors = Creasy CL, Chernoff J | title = Cloning and characterization of a human protein kinase with homology to Ste20 | journal = J. Biol. Chem. | volume = 270 | issue = 37 | pages = 21695–700 | year = 1995 | pmid = 7665586 | doi = 10.1074/jbc.270.37.21695 | doi-access = free }}
*{{cite journal | author=Gerber MJ, Drabkin HA, Firnhaber C, ''et al.'' |title=Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel. |journal=Am. J. Hum. Genet. |volume=43 |issue= 4 |pages= 442–51 |year= 1988 |pmid= 2902784 |doi= | pmc=1715492 }}
* {{cite journal | vauthors = Schultz SJ, Nigg EA | title = Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans | journal = Cell Growth Differ. | volume = 4 | issue = 10 | pages = 821–30 | year = 1993 | pmid = 8274451 }}
*{{cite journal | author=Creasy CL, Chernoff J |title=Cloning and characterization of a human protein kinase with homology to Ste20. |journal=J. Biol. Chem. |volume=270 |issue= 37 |pages= 21695–700 |year= 1995 |pmid= 7665586 |doi=10.1074/jbc.270.37.21695 }}
* {{cite journal | vauthors = Creasy CL, Chernoff J | title = Cloning and characterization of a member of the MST subfamily of Ste20-like kinases | journal = Gene | volume = 167 | issue = 1–2 | pages = 303–6 | year = 1995 | pmid = 8566796 | doi = 10.1016/0378-1119(95)00653-2 }}
*{{cite journal | author=Schultz SJ, Nigg EA |title=Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans. |journal=Cell Growth Differ. |volume=4 |issue= 10 |pages= 821–30 |year= 1994 |pmid= 8274451 |doi= }}
* {{cite journal | vauthors = Creasy CL, Ambrose DM, Chernoff J | title = The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain | journal = J. Biol. Chem. | volume = 271 | issue = 35 | pages = 21049–53 | year = 1996 | pmid = 8702870 | doi = 10.1074/jbc.271.35.21049 | doi-access = free }}
*{{cite journal | author=Creasy CL, Chernoff J |title=Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. |journal=Gene |volume=167 |issue= 1-2 |pages= 303–6 |year= 1996 |pmid= 8566796 |doi=10.1016/0378-1119(95)00653-2 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Res. | volume = 6 | issue = 9 | pages = 791–806 | year = 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
*{{cite journal | author=Creasy CL, Ambrose DM, Chernoff J |title=The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. |journal=J. Biol. Chem. |volume=271 |issue= 35 |pages= 21049–53 |year= 1996 |pmid= 8702870 |doi=10.1074/jbc.271.35.21049 }}
* {{cite journal | vauthors = Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S | title = MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19276–85 | year = 2001 | pmid = 11278283 | doi = 10.1074/jbc.M005109200 | doi-access = free }}
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Graves JD, Draves KE, Gotoh Y, Krebs EG, Clark EA | title = Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis | journal = J. Biol. Chem. | volume = 276 | issue = 18 | pages = 14909–15 | year = 2001 | pmid = 11278782 | doi = 10.1074/jbc.M010905200 | doi-access = free }}
*{{cite journal | author=Lee KK, Ohyama T, Yajima N, ''et al.'' |title=MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. |journal=J. Biol. Chem. |volume=276 |issue= 22 |pages= 19276–85 |year= 2001 |pmid= 11278283 |doi= 10.1074/jbc.M005109200 }}
* {{cite journal | vauthors = Lee KK, Yonehara S | title = Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST) | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 12351–8 | year = 2002 | pmid = 11805089 | doi = 10.1074/jbc.M108138200 | doi-access = free }}
*{{cite journal | author=Graves JD, Draves KE, Gotoh Y, ''et al.'' |title=Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis. |journal=J. Biol. Chem. |volume=276 |issue= 18 |pages= 14909–15 |year= 2001 |pmid= 11278782 |doi= 10.1074/jbc.M010905200 }}
* {{cite journal | vauthors = Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J | title = Identification of a novel Ras-regulated proapoptotic pathway | journal = Curr. Biol. | volume = 12 | issue = 4 | pages = 253–65 | year = 2002 | pmid = 11864565 | doi = 10.1016/S0960-9822(02)00683-8 | s2cid = 14053233 | doi-access = free }}
*{{cite journal | author=Deloukas P, Matthews LH, Ashurst J, ''et al.'' |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a }}
* {{cite journal | vauthors = De Souza PM, Kankaanranta H, Michael A, Barnes PJ, Giembycz MA, Lindsay MA | title = Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis | journal = Blood | volume = 99 | issue = 9 | pages = 3432–8 | year = 2002 | pmid = 11964314 | doi = 10.1182/blood.V99.9.3432 | doi-access = free }}
*{{cite journal | author=Lee KK, Yonehara S |title=Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). |journal=J. Biol. Chem. |volume=277 |issue= 14 |pages= 12351–8 |year= 2002 |pmid= 11805089 |doi= 10.1074/jbc.M108138200 }}
* {{cite journal | vauthors = Glantschnig H, Rodan GA, Reszka AA | title = Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation | journal = J. Biol. Chem. | volume = 277 | issue = 45 | pages = 42987–96 | year = 2002 | pmid = 12223493 | doi = 10.1074/jbc.M208538200 | doi-access = free }}
*{{cite journal | author=Khokhlatchev A, Rabizadeh S, Xavier R, ''et al.'' |title=Identification of a novel Ras-regulated proapoptotic pathway. |journal=Curr. Biol. |volume=12 |issue= 4 |pages= 253–65 |year= 2002 |pmid= 11864565 |doi=10.1016/S0960-9822(02)00683-8 }}
* {{cite journal | vauthors = Lin Y, Khokhlatchev A, Figeys D, Avruch J | title = Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis | journal = J. Biol. Chem. | volume = 277 | issue = 50 | pages = 47991–8001 | year = 2002 | pmid = 12384512 | doi = 10.1074/jbc.M202630200 | doi-access = free }}
*{{cite journal | author=De Souza PM, Kankaanranta H, Michael A, ''et al.'' |title=Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis. |journal=Blood |volume=99 |issue= 9 |pages= 3432–8 |year= 2002 |pmid= 11964314 |doi=10.1182/blood.V99.9.3432 }}
*{{cite journal | author=Glantschnig H, Rodan GA, Reszka AA |title=Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42987–96 |year= 2003 |pmid= 12223493 |doi= 10.1074/jbc.M208538200 }}
*{{cite journal | author=Lin Y, Khokhlatchev A, Figeys D, Avruch J |title=Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis. |journal=J. Biol. Chem. |volume=277 |issue= 50 |pages= 47991–8001 |year= 2003 |pmid= 12384512 |doi= 10.1074/jbc.M202630200 }}
*{{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 | pmc=139241 }}
}}
{{refend}}
{{refend}}

{{PDB Gallery|geneid=6789}}
{{PDB Gallery|geneid=6789}}


{{Serine/threonine-specific protein kinases}}
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
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[[Category:EC 2.7.11]]
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Latest revision as of 10:54, 17 October 2022

STK4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTK4, KRS2, MST1, TIIAC, YSK3, serine/threonine kinase 4
External IDsOMIM: 604965; MGI: 1929004; HomoloGene: 55965; GeneCards: STK4; OMA:STK4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006282
NM_001352385

NM_021420

RefSeq (protein)

NP_006273
NP_001339314

NP_067395

Location (UCSC)Chr 20: 44.97 – 45.08 MbChr 2: 163.91 – 164 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.[5][6][7]

Function

[edit]

The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p (sterile 20 protein) kinase, which acts upstream of the stress-induced mitogen-activated protein kinase (MAPK) cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process.[8]

Interactions

[edit]

STK4 has been shown to interact with PRKRIR.[9]

STK4 has also been shown to prevent, through Yap1 coactivator modulation, haematological tumor cell apoptosis.[10]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000101109Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018209Ensembl, 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. ^ Taylor LK, Wang HC, Erikson RL (November 1996). "Newly identified stress-responsive protein kinases, Krs-1 and Krs-2". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10099–104. Bibcode:1996PNAS...9310099T. doi:10.1073/pnas.93.19.10099. PMC 38343. PMID 8816758.
  6. ^ Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG (June 1998). "Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1". EMBO J. 17 (8): 2224–34. doi:10.1093/emboj/17.8.2224. PMC 1170567. PMID 9545236.
  7. ^ Ura S, Masuyama N, Graves JD, Gotoh Y (August 2001). "Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10148–53. Bibcode:2001PNAS...9810148U. doi:10.1073/pnas.181161698. PMC 56930. PMID 11517310.
  8. ^ "Entrez Gene: STK4 serine/threonine kinase 4".
  9. ^ Lin Y, Khokhlatchev A, Figeys D, Avruch J (December 2002). "Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis". J. Biol. Chem. 277 (50): 47991–8001. doi:10.1074/jbc.M202630200. PMID 12384512.
  10. ^ Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G (2014). "Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers" (PDF). Nat. Med. 20 (6): 599–606. doi:10.1038/nm.3562. PMC 4057660. PMID 24813251.

Further reading

[edit]