Home LiteratureArticle Details
PMID: 24833670 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Die another way--non-apoptotic mechanisms of cell death.

Journal of cell science ·Vol. 127 ·No. Pt 10 ·2014-05-15 ·Pages 2135-44

Tait SW, Ichim G, Green DR

Abstract

Regulated, programmed cell death is crucial for all multicellular organisms. Cell death is essential in many processes, including tissue sculpting during embryogenesis, development of the immune system and destruction of damaged cells. The best-studied form of programmed cell death is apoptosis, a process that requires activation of caspase proteases. Recently it has been appreciated that various non-apoptotic forms of cell death also exist, such as necroptosis and pyroptosis. These non-apoptotic cell death modalities can be either triggered independently of apoptosis or are engaged should apoptosis fail to execute. In this Commentary, we discuss several regulated non-apoptotic forms of cell death including necroptosis, autophagic cell death, pyroptosis and caspase-independent cell death. We outline what we know about their mechanism, potential roles in vivo and define outstanding questions. Finally, we review data arguing that the means by which a cell dies actually matters, focusing our discussion on inflammatory aspects of cell death.

Keywords
MLKL Mitochondria Necroptosis Pyroptosis RIPK3
MeSH Terms
Animals Apoptosis/physiology Autophagy/physiology Cell Death/physiology Humans
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tait Stephen W G
Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK stephen.tait@glasgow.ac.uk douglas.green@stjude.org.
Ichim Gabriel
Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK.
Green Douglas R
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA stephen.tait@glasgow.ac.uk douglas.green@stjude.org.
References (124)
124 references, click to expand
  1. Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization.
    EMBO J. 2003 Sep 1;22(17):4385-99 PMID: 12941691
  2. Cellular mechanisms controlling caspase activation and function.
    Cold Spring Harb Perspect Biol. 2013 Jun 01;5(6): PMID: 23732469
  3. Inflammasomes: far beyond inflammation.
    Nat Immunol. 2012 Mar 19;13(4):321-4 PMID: 22430784
  4. RIPK-dependent necrosis and its regulation by caspases: a mystery in five acts.
    Mol Cell. 2011 Oct 7;44(1):9-16 PMID: 21981915
  5. Diverse sequence determinants control human and mouse receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) interaction in necroptotic signaling.
    J Biol Chem. 2013 Jun 7;288(23):16247-16261 PMID: 23612963
  6. Virus inhibition of RIP3-dependent necrosis.
    Cell Host Microbe. 2010 Apr 22;7(4):302-313 PMID: 20413098
  7. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death.
    J Biol Chem. 2005 May 27;280(21):20722-9 PMID: 15778222
  8. Widespread mitochondrial depletion via mitophagy does not compromise necroptosis.
    Cell Rep. 2013 Nov 27;5(4):878-85 PMID: 24268776
  9. Calreticulin exposure dictates the immunogenicity of cancer cell death.
    Nat Med. 2007 Jan;13(1):54-61 PMID: 17187072
  10. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes.
    Nat Cell Biol. 2004 Dec;6(12):1221-8 PMID: 15558033
  11. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.
    Nat Immunol. 2010 Dec;11(12):1136-42 PMID: 21057511
  12. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein.
    J Virol. 1998 Nov;72(11):8586-96 PMID: 9765397
  13. Apoptotic and nonapoptotic caspase functions in animal development.
    Cold Spring Harb Perspect Biol. 2012 Oct 01;4(10): PMID: 23028118
  14. Butylated hydroxyanisole is more than a reactive oxygen species scavenger.
    Cell Death Differ. 2006 Jan;13(1):166-9 PMID: 16138110
  15. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
    Science. 2001 Apr 27;292(5517):727-30 PMID: 11326099
  16. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8.
    Science. 2004 Jun 4;304(5676):1500-2 PMID: 15131264
  17. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
    Science. 2011 Dec 16;334(6062):1573-7 PMID: 22174255
  18. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases.
    Immunity. 2009 Jul 17;31(1):84-98 PMID: 19559631
  19. Macrophage activation redirects yersinia-infected host cell death from apoptosis to caspase-1-dependent pyroptosis.
    PLoS Pathog. 2007 Nov;3(11):e161 PMID: 17983266
  20. It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival.
    Nat Rev Mol Cell Biol. 2011 Oct 21;12(11):757-63 PMID: 22016059
  21. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors.
    Nature. 1997 Apr 3;386(6624):517-21 PMID: 9087414
  22. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death.
    Cell. 2010 Aug 20;142(4):590-600 PMID: 20723759
  23. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism.
    Immunity. 2013 Sep 19;39(3):443-53 PMID: 24012422
  24. Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.
    Blood. 2007 Feb 15;109(4):1442-50 PMID: 17047155
  25. Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein.
    Immunity. 2008 Jul 18;29(1):21-32 PMID: 18631454
  26. Survival function of the FADD-CASPASE-8-cFLIP(L) complex.
    Cell Rep. 2012 May 31;1(5):401-7 PMID: 22675671
  27. Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death.
    Nat Rev Mol Cell Biol. 2013 Nov;14(11):727-36 PMID: 24129419
  28. The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event.
    J Cell Biol. 1999 Mar 8;144(5):883-9 PMID: 10085288
  29. Autophagy functions in programmed cell death.
    Autophagy. 2008 Apr;4(3):359-60 PMID: 18212526
  30. Necrotic death pathway in Fas receptor signaling.
    J Cell Biol. 2000 Dec 11;151(6):1247-56 PMID: 11121439
  31. Caspase functions in cell death and disease.
    Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a008656 PMID: 23545416
  32. Autophagic programmed cell death by selective catalase degradation.
    Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4952-7 PMID: 16547133
  33. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation.
    Nature. 2013 Jan 24;493(7433):547-51 PMID: 23235830
  34. Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment.
    J Cell Biol. 2009 Dec 28;187(7):1037-54 PMID: 20038679
  35. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1.
    EMBO J. 2007 May 16;26(10):2527-39 PMID: 17446862
  36. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012.
    Cell Death Differ. 2012 Jan;19(1):107-20 PMID: 21760595
  37. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation.
    Cell. 2007 Jun 1;129(5):983-97 PMID: 17540177
  38. Control of autophagic cell death by caspase-10 in multiple myeloma.
    Cancer Cell. 2013 Apr 15;23(4):435-49 PMID: 23541952
  39. Obatoclax (GX15-070) triggers necroptosis by promoting the assembly of the necrosome on autophagosomal membranes.
    Cell Death Differ. 2013 Sep;20(9):1161-73 PMID: 23744296
  40. Autophagy, not apoptosis, is essential for midgut cell death in Drosophila.
    Curr Biol. 2009 Nov 3;19(20):1741-6 PMID: 19818615
  41. Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells.
    Dev Cell. 2013 Dec 23;27(6):621-34 PMID: 24369835
  42. Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity.
    J Gen Virol. 2013 Nov;94(Pt 11):2367-2392 PMID: 23999164
  43. Autophagic cell death: the story of a misnomer.
    Nat Rev Mol Cell Biol. 2008 Dec;9(12):1004-10 PMID: 18971948
  44. Immunogenic and tolerogenic cell death.
    Nat Rev Immunol. 2009 May;9(5):353-63 PMID: 19365408
  45. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha.
    Cell. 2009 Jun 12;137(6):1100-11 PMID: 19524512
  46. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.
    Nat Immunol. 2000 Dec;1(6):489-95 PMID: 11101870
  47. TNF-alpha induces two distinct caspase-8 activation pathways.
    Cell. 2008 May 16;133(4):693-703 PMID: 18485876
  48. Autophagy gene disruption reveals a non-vacuolar cell death pathway in Dictyostelium.
    J Biol Chem. 2004 Nov 12;279(46):48404-9 PMID: 15358773
  49. Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL.
    Cell Death Differ. 2010 Feb;17(2):268-77 PMID: 19713971
  50. Pyroptosis: host cell death and inflammation.
    Nat Rev Microbiol. 2009 Feb;7(2):99-109 PMID: 19148178
  51. Protective roles for caspase-8 and cFLIP in adult homeostasis.
    Cell Rep. 2013 Oct 31;5(2):340-8 PMID: 24095739
  52. RIP3 mediates the embryonic lethality of caspase-8-deficient mice.
    Nature. 2011 Mar 17;471(7338):368-72 PMID: 21368762
  53. Switch from caspase-dependent to caspase-independent death during heart development: essential role of endonuclease G in ischemia-induced DNA processing of differentiated cardiomyocytes.
    J Biol Chem. 2006 Aug 11;281(32):22943-52 PMID: 16754658
  54. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy.
    J Cell Biol. 2008 Dec 1;183(5):795-803 PMID: 19029340
  55. Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice.
    Nature. 2003 Oct 16;425(6959):721-7 PMID: 14534547
  56. Dissecting p53 tumor suppressor functions in vivo.
    Cancer Cell. 2002 Apr;1(3):289-98 PMID: 12086865
  57. Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis.
    Mol Biol Cell. 2008 Aug;19(8):3576-88 PMID: 18550800
  58. Autophagy activity contributes to programmed cell death in Caenorhabditis elegans.
    Autophagy. 2013 Dec;9(12):1975-82 PMID: 24185352
  59. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
    J Immunol. 1988 Oct 15;141(8):2629-34 PMID: 3171180
  60. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms.
    Mol Cell. 2011 Aug 5;43(3):449-63 PMID: 21737330
  61. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.
    Cell. 1992 May 15;69(4):597-604 PMID: 1339309
  62. Apaf1 is required for mitochondrial pathways of apoptosis and brain development.
    Cell. 1998 Sep 18;94(6):739-50 PMID: 9753321
  63. Intra-mitochondrial degradation of Tim23 curtails the survival of cells rescued from apoptosis by caspase inhibitors.
    Cell Death Differ. 2008 Mar;15(3):545-54 PMID: 18174902
  64. Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome.
    Immunity. 2013 Jan 24;38(1):27-40 PMID: 23260196
  65. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.
    Cell. 2005 Sep 23;122(6):927-39 PMID: 16179260
  66. Resistance to caspase-independent cell death requires persistence of intact mitochondria.
    Dev Cell. 2010 May 18;18(5):802-13 PMID: 20493813
  67. Regulation and function of autophagy during cell survival and cell death.
    Cold Spring Harb Perspect Biol. 2012 Jun 01;4(6): PMID: 22661635
  68. Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain.
    Cell Signal. 2007 Oct;19(10):2056-67 PMID: 17644308
  69. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis.
    Nat Cell Biol. 2006 Oct;8(10):1124-32 PMID: 16998475
  70. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation.
    Immunity. 2011 Oct 28;35(4):572-82 PMID: 22000287
  71. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis.
    Cell. 2012 Jul 20;150(2):339-50 PMID: 22817896
  72. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs.
    Mol Cell. 2011 Aug 5;43(3):432-48 PMID: 21737329
  73. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA.
    Cell Host Microbe. 2012 Mar 15;11(3):290-7 PMID: 22423968
  74. Steroid regulated programmed cell death during Drosophila metamorphosis.
    Development. 1997 Nov;124(22):4673-83 PMID: 9409683
  75. Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development.
    Cell. 1998 Sep 18;94(6):727-37 PMID: 9753320
  76. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages.
    Cell Microbiol. 2006 Nov;8(11):1812-25 PMID: 16824040
  77. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation.
    Immunity. 2012 Feb 24;36(2):215-27 PMID: 22365665
  78. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis.
    Nature. 2011 Mar 17;471(7338):363-7 PMID: 21368763
  79. NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-α feedforward signaling.
    Cell. 2011 Apr 1;145(1):92-103 PMID: 21458669
  80. Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.
    Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20364-71 PMID: 24277826
  81. TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1.
    Cell Death Dis. 2013 Jan 17;4:e465 PMID: 23328672
  82. Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.
    PLoS One. 2012;7(7):e41831 PMID: 22848625
  83. Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c.
    Nat Cell Biol. 2008 Dec;10(12):1477-83 PMID: 19029908
  84. Autophagy in human health and disease.
    N Engl J Med. 2013 May 9;368(19):1845-6 PMID: 23656658
  85. Antigen-mediated T cell expansion regulated by parallel pathways of death.
    Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17463-8 PMID: 18981423
  86. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.
    Cell. 2012 Jan 20;148(1-2):213-27 PMID: 22265413
  87. Adult Apaf-1-deficient mice exhibit male infertility.
    Dev Biol. 2000 Feb 15;218(2):248-58 PMID: 10656767
  88. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation.
    Cell. 2009 Jun 12;137(6):1112-23 PMID: 19524513
  89. Caspase-independent mitochondrial cell death results from loss of respiration, not cytotoxic protein release.
    Mol Biol Cell. 2009 Dec;20(23):4871-84 PMID: 19793916
  90. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway.
    Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20054-9 PMID: 22123964
  91. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis.
    J Cell Sci. 2009 Jul 15;122(Pt 14):2554-66 PMID: 19549685
  92. Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration.
    Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11573-8 PMID: 16864784
  93. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation.
    J Biol Chem. 1992 Mar 15;267(8):5317-23 PMID: 1312087
  94. How dying cells alert the immune system to danger.
    Nat Rev Immunol. 2008 Apr;8(4):279-89 PMID: 18340345
  95. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.
    Nat Chem Biol. 2005 Jul;1(2):112-9 PMID: 16408008
  96. Non-canonical inflammasome activation targets caspase-11.
    Nature. 2011 Oct 16;479(7371):117-21 PMID: 22002608
  97. Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum.
    J Biol Chem. 2003 May 16;278(20):17636-45 PMID: 12626495
  98. Interdigital cell death can occur through a necrotic and caspase-independent pathway.
    Curr Biol. 1999 Sep 9;9(17):967-70 PMID: 10508592
  99. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival.
    Mol Cell. 2011 Apr 8;42(1):23-35 PMID: 21353614
  100. RIP3: a molecular switch for necrosis and inflammation.
    Genes Dev. 2013 Aug 1;27(15):1640-9 PMID: 23913919
  101. Autophagy in protein and organelle turnover.
    Cold Spring Harb Symp Quant Biol. 2011;76:397-402 PMID: 21813637
  102. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis.
    Science. 2009 Jul 17;325(5938):332-6 PMID: 19498109
  103. Necroptosis in immunity and ischemia-reperfusion injury.
    Am J Transplant. 2013 Nov;13(11):2797-804 PMID: 24103029
  104. Caspase-independent cell death: leaving the set without the final cut.
    Oncogene. 2008 Oct 27;27(50):6452-61 PMID: 18955972
  105. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation.
    Nature. 2011 Jul 31;477(7364):330-4 PMID: 21804564
  106. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis.
    Cell Res. 2013 Aug;23(8):994-1006 PMID: 23835476
  107. A perspective on mammalian caspases as positive and negative regulators of inflammation.
    Mol Cell. 2012 May 25;46(4):387-97 PMID: 22633487
  108. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis.
    Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5322-7 PMID: 22421439
  109. Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways.
    Immunity. 2011 Oct 28;35(4):445-55 PMID: 22035837
  110. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis.
    Cell. 2006 Jul 14;126(1):121-34 PMID: 16839881
  111. Bim inhibits autophagy by recruiting Beclin 1 to microtubules.
    Mol Cell. 2012 Aug 10;47(3):359-70 PMID: 22742832
  112. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.
    Science. 2014 Mar 21;343(6177):1357-60 PMID: 24557836
  113. Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4312-7 PMID: 18337499
  114. Apoptosis: controlled demolition at the cellular level.
    Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41 PMID: 18073771
  115. The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1.
    Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2396-401 PMID: 10051653
  116. Programmed necrosis from molecules to health and disease.
    Int Rev Cell Mol Biol. 2011;289:1-35 PMID: 21749897
  117. Caspase 8 inhibits programmed necrosis by processing CYLD.
    Nat Cell Biol. 2011 Oct 30;13(12):1437-42 PMID: 22037414
  118. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death.
    Cell Res. 2014 Jan;24(1):105-21 PMID: 24366341
  119. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis.
    Nat Cell Biol. 2014 Jan;16(1):55-65 PMID: 24316671
  120. Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons.
    J Cell Biol. 2007 Dec 3;179(5):825-32 PMID: 18056406
  121. cFLIP regulates skin homeostasis and protects against TNF-induced keratinocyte apoptosis.
    Cell Rep. 2013 Oct 31;5(2):397-408 PMID: 24209745
  122. Evidence of a novel event during neuronal death: development of competence-to-die in response to cytoplasmic cytochrome c.
    Neuron. 1998 Oct;21(4):695-705 PMID: 9808457
  123. Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function.
    Oncogene. 2009 May 28;28(21):2128-41 PMID: 19347031
  124. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways.
    Cell. 2012 Jan 20;148(1-2):228-43 PMID: 22265414
Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
1477-9137
DOI
10.1242/jcs.093575
Email
stephen.tait@glasgow.ac.uk
douglas.green@stjude.org
Published
2014-05-15
Pages
2135-44
Language
English
Region
England
NLM ID
0052457
PMCID
PMC4021468
Subset
IM
Grants
NIAID NIH HHS · R01 AI044828 · United States
NIGMS NIH HHS · R01 GM096208 · United States
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1242/jcs.093575 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2