Molecular Biology

, Volume 52, Issue 5, pp 648–659 | Cite as

Caspase-2 as an Oncosupressor and Metabolism Regulator: What Life Will Bring over the Long Run?

  • A. Yu. Egorshina
  • A. V. Zamaraev
  • I. N. Lavrik
  • B. D. Zhivotovsky
  • G. S. Kopeina


Programmed cell death is governed by a set of gene networks, which define a variety of distinct molecular mechanisms essential for the maintenance of multicellular organisms. The most studied modality of programmed cell death is known as apoptosis. Caspase-2, as a member of the family of the cysteine-dependent protease, demonstrates both proapoptotic and tumor suppressive functions. This protease plays an essential role in the maintenance of genomic stability and induces apoptotic cell death in response to genotoxic stress. Here we discuss the molecular mechanisms of caspase-2 regulation and its physiological role as a tumor suppressor and metabolic regulator.


apoptosis caspase-2 tumor suppressor metabolism 


This work was supported by grant from the Russian Science Foundation (17-75-20102). The work in the authors’ laboratories is also supported by grants from the Russian Foundation for Basic Research (18-015-00211, 18-04-00207), the Swedish (160 733) and the Stockholm Cancer Societies (161 292; The Stockholm and Swedish Cancer Societies), the Swedish Childhood Cancer Foundation (PR2016-0090) and the Swedish Research Council (521-2014-2258).


  1. 1.
    Kerr J.F., Wyllie A.H., Currie A.R. 1972. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 26, 239–257.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Olsson M., Zhivotovsky B. 2011. Caspases and cancer. Cell Death Differ. 18, 1441–1449.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zamaraev A.V., Kopeina G.S., Zhivotovsky B., Lavrik I.N. 2015. Cell death controlling complexes and their potential therapeutic role. Cell Mol. Life Sci. 72, 505–517.CrossRefPubMedGoogle Scholar
  4. 4.
    Imre G., Heering J., Takeda A.N., Husmann M., Thiede B., zu Heringdorf D.M., Green D.R., van der Goot F.G., Sinha B., Dötsch V., Rajalingam K. 2012. Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis. EMBO J. 31, 2615–2628.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Aksenova V.I., Bylino O.V., Zhivotovsky B.D., Lavrik I.N. 2013. Caspase-2: What do we know today? 47, 165–180.Google Scholar
  6. 6.
    Yuan J., Shaham S., Ledoux S., Ellis H.M., Horvitzt H.R. 1993. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme. Cell. 75, 641–652.CrossRefPubMedGoogle Scholar
  7. 7.
    Baliga B.C., Read S.H., Kumar S. 2004. The biochemical mechanism of caspase-2 activation. Cell Death Differ. 11, 1234–1241.CrossRefPubMedGoogle Scholar
  8. 8.
    Baliga B.C., Colussi P.A., Read S.H., Dias M.M., Jans D.A., Kumar S. 2003. Role of prodomain in importin-mediated nuclear localization and activation of caspase-2. J. Biol. Chem. 278, 4899–4905.CrossRefPubMedGoogle Scholar
  9. 9.
    Wang L., Miura M., Bergeron L., Zhu H., Yuan J. 1994. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 78, 739–750.CrossRefPubMedGoogle Scholar
  10. 10.
    Schwerk C., Schulze-Osthoff K. 2005. Regulation of apoptosis by alternative pre-mRNA splicing. Mol. Cell. 19, 1–13.CrossRefPubMedGoogle Scholar
  11. 11.
    Upton J.P., Austgen K., Nishino M., Coakley K.M., Hagen A., Han D., Papa F.R., Oakes S.A. 2008. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol. Cell Biol. 28, 3943–3951.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wagner K.W., Engels I.H., Deveraux Q.L. 2004. Caspase-2 can function upstream of Bid cleavage in the TRAIL apoptosis pathway. J. Biol. Chem. 279, 35 047–35 052.CrossRefGoogle Scholar
  13. 13.
    Krumschnabel G., Sohm B., Bock F., Manzl C., Villunger A. 2009. The enigma of caspase-2: The laymen’s view. Cell Death Differ. 16, 195–207.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhivotovsky B., Orrenius S. 2005. Caspase-2 function in response to DNA damage. Biochem. Biophys. Res. Commun. 331, 859–867.CrossRefPubMedGoogle Scholar
  15. 15.
    Talanian R.V., Quinlan C., Trautz S., Hackett M.C., Mankovich J.A., Banach D., Ghayur T., Brady K.D., Wong W.W. 1997. Substrate specificities of caspase family proteases. J. Biol. Chem. 272, 9677–9682.CrossRefPubMedGoogle Scholar
  16. 16.
    Miles M.A., Kitevska-Ilioski T., Hawkins C.J. 2017. Old and novel functions of caspase-2. Int. Rev. Cell Mol. Biol. 332, 155–212.CrossRefPubMedGoogle Scholar
  17. 17.
    Fava L.L., Bock F.J., Geley S., Villunger A. 2012. Caspase-2 at a glance. J. Cell Sci. 125, 5911–5915.CrossRefPubMedGoogle Scholar
  18. 18.
    Brynychová V., Hlaváč V., Ehrlichová M., Václavíková R., Pecha V., Trnková M., Wald M., Mrhalová M., Kubáčková K., Pikus T., Kodet R., Kovář J., Souček P. 2013. Importance of transcript levels of caspase-2 isoforms S and L for breast carcinoma progression. Future Oncol. 9, 427–438.CrossRefPubMedGoogle Scholar
  19. 19.
    Mancini M., Machamer C.E., Roy S., Nicholson D.W., Thornberry N.A., Casciola-Rosen L.A., Rosen A. 2000. Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J. Cell Biol. 149, 603–612.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zhivotovsky B., Samali A., Gahm A., Orrenius S. 1999. Caspases: Their intracellular localization and translocation during apoptosis. Cell Death Differ. 6, 644–651.CrossRefPubMedGoogle Scholar
  21. 21.
    Tinel A., Tschopp J. 2004. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science. 304, 843–846.CrossRefPubMedGoogle Scholar
  22. 22.
    Lavrik I.N., Golks A., Baumann S., Krammer P.H. 2006. Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis. Blood. 108, 559–565.CrossRefPubMedGoogle Scholar
  23. 23.
    Thome M., Hofmann K., Burns K., Martinon F., Bodmer J.L., Mattmann C., Tschopp J. 1998. Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. Curr. Biol. 8, 885–888.CrossRefPubMedGoogle Scholar
  24. 24.
    Manzl C., Krumschnabel G., Bock F., Sohm B., Labi V., Baumgartner F., Logette E., Tschopp J., Villunger A. 2009. Caspase-2 activation in the absence of PIDDosome formation. J. Cell Biol. 185, 291–303.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kopeina G.S., Zamaraev A.V., Zhivotovsky B.D., Lavrik I.N. 2016. Identification of new complex for caspase-2 activation after DNA damage. Russ. J. Bioorg. Chem. 42, 74–82.CrossRefGoogle Scholar
  26. 26.
    Ando K., Kernan J.L., Liu P.H., Sanda T., Logette E., Tschopp J., Look A.T., Wang J., Bouchier-Hayes L., Sidi S. 2012. PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. Mol. Cell. 47, 681–693.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Park H.H., Logette E., Raunser S., Cuenin S., Walz T., Tschopp J., Wu H. 2007. Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex. Cell. 128, 533–546.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ando K., Parsons M.J., Shah R.B., Charendoff C.I., Paris S.L., Liu P.H., Fassio S.R., Rohrman B.A., Thompson R., Oberst A., Sidi S., Bouchier-Hayes L. 2017. NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus. J. Cell Biol. 216, 1795–1810.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Dawar S., Lim Y., Puccini J., White M., Thomas P., Bouchier-Hayes L., Green D.R., Dorstyn L., Kumar S. 2017. Caspase-2-mediated cell death is required for deleting aneuploid cells. Oncogene. 36, 2704–2714.CrossRefPubMedGoogle Scholar
  30. 30.
    Fava L.L., Schuler F., Sladky V., Haschka M.D., Soratroi C., Eiterer L., Demetz E., Weiss G., Geley S., Nigg E.A., Villunger A. 2017. The PIDDosome activates p53 in response to supernumerary centrosomes. Genes. Dev. 31, 34–45.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sidi S., Sanda T., Kennedy R.D., Hagen A.T., Jette C.A., Hoffmans R., Pascual J., Imamura S., Kishi S., Amatruda J.F., Kanki J.P., Green D.R., D’Andrea A.A., Look A.T. 2008. Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3. Cell. 133, 864–877.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Thompson R., Shah R.B., Liu P.H., Gupta Y.K., Ando K., Aggarwal A.K., Sidi S. 2014. An inhibitor of PIDDosome formation. Mol. Cell. 58, 767–779.CrossRefGoogle Scholar
  33. 33.
    Di Donato N., Jean Y.Y., Maga A.M., Krewson B.D., Shupp A.B., Avrutsky M.I., Roy A., Collins S., Olds C., Willert R.A., Czaja A.M., Johnson R., Stover J.A., Gottlieb S., Bartholdi D., et al. 2016. Mutations in CRADD result in reduced caspase-2-mediated neuronal apoptosis and cause megalencephaly with a rare lissencephaly variant. Am. J. Hum. Genet. 99, 1117–1129.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhao X., Kotilinek L.A., Smith B., Hlynialuk C., Zahs K., Ramsden M., Cleary J., Ashe K.H. 2016. Caspase-2 cleavage of tau reversibly impairs memory. Nat. Med. 22, 1268–1276.CrossRefPubMedGoogle Scholar
  35. 35.
    Imre G., Berthelet J., Heering J., Kehrloesser S., Melzer I.M., Lee B.I., Thiede B., Dötsch V., Rajalingam K. 2017. Apoptosis inhibitor 5 is an endogenous inhibitor of caspase-2. EMBO Rep. 18, 733–744.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bronner D.N., Abuaita B.H., Chen X., Fitzgerald K.A., Nuñez G., He Y., Yin X.M., O’Riordan M.X. 2015. Endoplasmic reticulum stress activates the inflammasome via NLRP3- and caspase-2-driven mitochondrial damage. Immunity. 43, 451–462.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Forsberg J., Li X., Akpinar B., Salvatori R., Ott M., Zhivotovsky B., Olsson M. 2018. A caspase-2-RFXANK interaction and its implication for MHC class II expression. Cell Death Dis. 9, 80. doi 10.1038/s41419-017-0144-yCrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Chen F., Ding X., Ding Y., Xiang Z., Li X., Ghosh D., Schurig G.G., Sriranganathan N., Boyle S.M., He Y. 2011. Proinflammatory caspase-2-mediated macrophage cell death induced by a rough attenuated brucella suis strain. Infect. Immun. 79, 2460–2469.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Li X., He Y. 2012. Caspase-2-dependent dendritic cell death, maturation, and priming of T cells in response to Brucella abortus infection. PLoS One. 7, e43512.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zamaraev A.V., Kopeina G.S., Prokhorova E.A., Zhivotovsky B., Lavrik I.N. 2017. Post-translational modification of caspases: The other side of apoptosis regulation. Trends Cell Biol. 27, 322–339.CrossRefPubMedGoogle Scholar
  41. 41.
    Nutt L.K., Margolis S.S., Jensen M., Herman C.E., Dunphy W.G., Rathmell J.C., Kornbluth S. 2005. Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell. 123, 89–103.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Nutt L.K., Buchakjian M.R., Gan E., Darbandi R., Yoon S.Y., Wu J.Q., Miyamoto Y.J., Gibbons J.A., Andersen J.L., Freel C.D., Tang W., He C., Kurokawa M., Wang Y., Margolis S.S., et al. 2009. Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2. Dev. Cell. 16, 856–866.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Andersen J.L., Johnson C.E., Freel C.D., Parrish A.B., Day J.L., Buchakjian M.R., Nutt L.K., Thompson J.W., Moseley M.A., Kornbluth S. 2009. Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2. EMBO J. 28, 3216–3227.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K. 2010. Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity. Mol. Cell Biol. 30, 5726–5740.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Allan L.A., Clarke P.R. 2007. Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis. Mol. Cell. 26, 301–310.CrossRefPubMedGoogle Scholar
  46. 46.
    Yi C.H., Sogah D.K., Boyce M., Degterev A., Christofferson D.E., Yuan J. 2007. A genome-wide RNAi screen reveals multiple regulators of caspase activation. J. Cell Biol. 179, 619–626.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Shin S., Lee Y., Kim W., Ko H., Choi H., Kim K. 2005. Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J. 24, 3532–3542.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Shirakura H., Hayashi N., Ogino S., Tsuruma K., Uehara T., Nomura Y. 2005. Caspase recruitment domain of procaspase-2 could be a target for SUMO-1 modification through Ubc9. Biochem. Biophys. Res. Commun. 331, 1007–1015.CrossRefPubMedGoogle Scholar
  49. 49.
    Mendelsohn A.R., Hamer J.D., Wang Z.B., Brent R. 2002. Cyclin D3 activates caspase 2, connecting cell proliferation with cell death. Proc. Natl. Acad. Sci. U. S. A. 99, 6871–6876.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Castedo M., Perfettini J.-L., Roumier T., Valent A., Raslova H., Yakushijin K., Horne D., Feunteun J., Lenoir G., Medema R., Vainchenker W., Kroemer G. 2004. Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy. Oncogene. 23, 4362–4370.CrossRefPubMedGoogle Scholar
  51. 51.
    Dorstyn L., Puccini J., Wilson C.H., Shalini S., Nicola M., Moore S., Kumar S. 2012. Caspase-2 deficiency promotes aberrant DNA-damage response and genetic instability. Cell Death Differ. 19, 1288–1298.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Shalini S., Puccini J., Wilson C.H, Finnie J., Dorstyn L., Kumar S. 2014. Caspase-2 protects against oxidative stress in vivo. Oncogene. 34, 4995–5002.CrossRefPubMedGoogle Scholar
  53. 53.
    López-García C., Sansregret L., Domingo E., McGranahan N., Hobor S., Birkbak N.J., Horswell S., Grönroos E., Favero F., Rowan A.J., Matthews N., Begum S., Phillimore B., Burrell R., Oukrif D., et al. 2017. BCL9L dysfunction impairs caspase-2 expression permitting aneuploidy tolerance in colorectal cancer. Cancer Cell. 31, 79–93.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Vassilev L.T., Vu B.T., Graves B., Carvajal D., Podlaski F., Filipovic Z., Kong N., Kammlott U., Lukacs C., Klein C., Fotouhi N., Liu E.A. 2004. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303, 844–848.CrossRefPubMedGoogle Scholar
  55. 55.
    Prives C. 1998. Signaling to p53: Breaking the MDM2-p53 circuit. Cell. 95, 5–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Lopez-Cruzan M., Sharma R., Tiwari M., Karbach S., Holstein D., Martin C.R., Lechleiter J.D., Herman B. 2016. Caspase-2 resides in the mitochondria and mediates apoptosis directly from the mitochondrial compartment. Cell Death Discov. 2, 16005. doi 10.1038/cddiscovery.2016.5CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Peintner L., Dorstyn L., Kumar S., Aneichyk T., Villunger A., Manzl C. 2015. The tumor-modulatory effects of caspase-2 and Pidd1 do not require the scaffold protein Raidd. Cell Death Differ. 22, 1803–1811.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Holleman A., den Boer M.L., Kazemier K.M., Be-verloo H.B., von Bergh A.R., Janka-Schaub G.E., Pieters R. 2005. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia. Blood. 106, 1817–1823.CrossRefPubMedGoogle Scholar
  59. 59.
    Yoo N.J., Lee J.W., Kim Y.J., Soung Y.H., Kim S.Y., Nam S.W., Park W.S., Lee J.Y., Lee S.H. (2004. Loss of caspase-2, -6 and -7 expression in gastric cancers. APMIS. 112, 330–335.CrossRefPubMedGoogle Scholar
  60. 60.
    Zohrabian V.M., Nandu H., Gulati N., Khitrov G., Zhao C., Mohan A., Demattia J., Braun A., Das K., Murali R., Jhanwar-Uniyal M. 2007. Gene expression profiling of metastatic brain cancer. Oncol. Rep. 18, 321–328.PubMedGoogle Scholar
  61. 61.
    Dorstyn L., Puccini J., Nikolic A., Shalini S., Wilson C.H., Norris M.D., Haber M., Kumar S. 2014. An unexpected role for caspase-2 in neuroblastoma. Cell Death Dis. 5, e1383.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Kumar S., White D.L., Takai S., Turczynowicz S., Juttner C.A., Hughes T.P. 1995. Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms. Hum. Genet. 95, 641–644.CrossRefPubMedGoogle Scholar
  63. 63.
    Honda H., Nagamachi A., Inaba T. 2015. –7/7q– syndrome in myeloid-lineage hematopoietic malignancies: Attempts to understand this complex disease entity. Oncogene. 34, 2413–2425.CrossRefPubMedGoogle Scholar
  64. 64.
    da Silva F.B., Machado-Neto J.A., Bertini V.H.L.L., Velloso E.D.R.P., Ratis C.A., Calado R.T., Simões B.P., Rego E.M., Traina F. 2017. Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome. J. Clin. Pathol. 70, 435–442.CrossRefPubMedGoogle Scholar
  65. 65.
    Kim M.S., Kim H.S., Jeong E.G., Soung Y.H., Yoo N.J., Lee S.H. 2011. Somatic mutations of caspase-2 gene in gastric and colorectal cancers. Pathol. Res. Pract. 207, 640–644.CrossRefPubMedGoogle Scholar
  66. 66.
    Ren K., Lu J., Porollo A., Du C. 2012. Tumor-suppressing function of caspase-2 requires catalytic site Cys-320 and site Ser-139 in mice. J. Biol. Chem. 287, 14 792–14 802.CrossRefGoogle Scholar
  67. 67.
    Parsons M.J., McCormick L., Janke L., Howard A., Bouchier-Hayes L., Green D.R. 2013. Genetic deletion of caspase-2 accelerates MMTV/c-neu-driven mammary carcinogenesis in mice. Cell Death Differ. 20, 1174–1182.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Shalini S., Nikolic A., Wilson C.H., Puccini J., Sladojevic N., Finnie J., Dorstyn L., Kumar S. 2016. Caspase-2 deficiency accelerates chemically induced liver cancer in mice. Cell Death Differ. 23, 1727–1736.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Puccini J., Dorstyn L., Kumar S. 2013. Caspase-2 as a tumour suppressor. Cell Death Differ. 20, 1133–1139.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Oliver T.G., Meylan E., Chang G.P., Xue W., Burke J.R., Humpton T.J., Hubbard D., Bhutkar A., Jacks T. 2011. Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop. Mol. Cell. 43, 57–71.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Terry M.R., Arya R., Mukhopadhyay A., Berrett K.C., Clair P.M., Witt B., Salama M.E., Bhutkar A., Oliver T.G. 2015. Caspase-2 impacts lung tumorigenesis and chemotherapy response in vivo. Cell Death Differ. 22, 719–730.CrossRefPubMedGoogle Scholar
  72. 72.
    Johnson E.S., Lindblom K.R., Robeson A., Stevens R.D., Ilkayeva O.R., Newgard C.B., Kornbluth S., Andersen J.L. 2013. Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis. J. Biol. Chem. 288, 14 463–14 475.CrossRefGoogle Scholar
  73. 73.
    Machado M.V., Michelotti G.A., Jewell M.L., Pereira T.A., Xie G., Premont RT., Diehl A.M. 2016. Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease. Cell Death Dis. 7, e2096.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Wilson C.H., Nikolic A., Kentish S.J., Keller M., Hatzinikolas G., Dorstyn L., Page A.J., Kumar S. 2017. Caspase-2 deficiency enhances whole-body carbohydrate utilisation and prevents high-fat diet-induced obesity. Cell Death Dis. 8, e3136.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Wilson C.H., Shalini S., Filipovska A., Richman T.R., Davies S., Martin S.D., McGee S.L., Puccini J., Nikolic A., Dorstyn L., Kumar S. 2015. Age-related proteostasis and metabolic alterations in caspase-2-deficient mice. Cell Death Dis. 6, e1615.CrossRefPubMedGoogle Scholar
  76. 76.
    Wilson C.H., Dorstyn L., Kumar S. 2016. Fat, sex and caspase-2. Cell Death Dis. 7, e2125.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Wilson C., Nikolic A., Kentish S., Shalini S., Hatzinikolas G., Page A.J., Dorstyn L., Kumar S. 2016. Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice. Cell Death Discov. 2, 16 009.CrossRefGoogle Scholar
  78. 78.
    Tiwari M., Lopez-Cruzan M., Morgan W.W., Herman B. 2011. Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J. Biol. Chem. 286, 8493–8506.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Tiwari M., Sharma L.K., Vanegas D, Callaway D.A., Bai Y., Lechleiter J.D., Herman B. 2014. A nonapoptotic role for CASP2/caspase 2: Modulation of autophagy. Autophagy. 10, 1054–1070.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  1. 1.Faculty of Basic Medicine, Moscow State UniversityMoscowRussia
  2. 2.Medical Faculty, Otto von Guericke UniversityMagdeburgGermany
  3. 3.Karolinska InstitutetStockholmSweden

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