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Otofaji: Bir Hücresel Stres Yanıtı ve Ölüm Mekanizması

Year 2011, Issue: 4, 184 - 194, 01.12.2011

Devrim Öz Arslan Gözde Korkmaz Devrim Gözüaçık

Abstract

Otofaji uzun ömürlü proteinlerin, organellerin ve sitoplazmik parçacıkların parçalanmasından sorumlu fizyolojik bir fenomendir. Otofaji, lizozomal parçalanmadan sonra hücresel geridönüşümü sağlar ve hücrenin açlık, büyüme faktörü yokluğu ve oksidatif stres gibi çeşitli koşullarda hayatta kalmasına yardımcı olur. Paradoksal olarak bazı koşullar altında otofaji hücreyi kaspaz bağımsız yolak üzerinden, apoptotik olmayan hücre ölümüyle, öldürebilmektedir Tip II hücre ölümü ya da otofajik hücre ölümü . Birçok veri, klasik apoptoz ile otofaji arasında doğrudan bir bağlantı olduğunu işaret etmektedir ve bu bağlantı moleküler düzeyde aydınlatılmaya başlanmıştır. Apoptoz ve otofaji arasındaki karşılıklı etkileşim oldukça karışık gibi gözükmektedir. Fakat bu alandaki araştırmalar kanser, enfeksiyonlar ve nörodejenaratif hastalıklar gibi sağlık problemleri için yeni tanı, takip ve tedavi yöntemlerine yol açma potansiyeli nedeniyle çok büyük önem arz etmektedir

Keywords

Otofaji apoptoz hayatta kalım sinyal iletimi

References

  • Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol 2001;2:211-6.
  • Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science 2004;306:990-5.
  • Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-75.
  • Yang Z, Klionsky D. Eaten alive: a history of macroautophagy. Nat Cell Biol 2010;12:814-822.
  • Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptaion. Nat Cell Biol 2007;9:1102-9.
  • Kroemer G, Marino G, Levine B. Autophagy and integrated stress response. Mol Cell 2010;40(2):280-293.
  • Mehrpour M, Esclatine A, Beau I, Codogno P. Overwiew of macroautophagy regulation in mammalian cells. Cell Research 2010;20:748-762.
  • Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 2000; 150:1507-13.
  • Shang L, Wang X. AMPK and mTOR coordinate the regulation of Ulk1 and mammalian autophagy initiation. Autophagy 2011;7(8):924-6.
  • Scott RC, Schuldiner O, Neufeld TP. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell 2004;7:167-8.
  • Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature 2001;411:355-65.
  • Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 2004;36:2445-62.
  • Ari co S, Petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P, Ogier-Denis E. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 2001; 276:35243-6.
  • Lia ng XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402:672-6.
  • Pfisterer SG, Mauthe M, Codogno P, Proikas-Cezanne T. Ca2+/Calmodulin-dependent kinase signaling via CaMKI and AMPK contributes to the regulation of WIPI-1 at the onset of autophagy. Molecular Pharmacology September 6, 2011 doi:10.1124/mol.111.071761
  • Ogi er-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, Isidoro C, Laburthe M, Codogno P. A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29. J Biol Chem 1995;270:13-16.
  • Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol 2002;157:455-8.
  • chromosomal instability. Genes Dev 2007;21:1367–81.
  • Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan R. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 2007;128:931-46.
  • Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M. Autophagy is involved in T cell death after binding of HIV envelope proteins to CXCR4. J Clin Invest 2006;116: 2161.
  • Corradetti M, Guan K. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 2006;25:6347–60.
  • Guertin D, Sabatini D. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9–22.
  • Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 2005;9:59–71.
  • McCubrey J, Steelman L, Chap pell W, Abrams S, Wong E, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007;1773:1263–84.
  • Ballif B, Blenis J. Molecular m echanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPk survival signals. Cell Growth Diff 2001;12: 397–408.
  • Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008;4:600-6.
  • Noble C, Dong J, Manser E, Song H. BCL-XL and UVRAG cause a monomer-dimer switch in beclin1. J Biol Chem 2008;283:26274–82.
  • Mellor HR, Harris AL. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. Cancer Metastasis Rev 2007;26:553-66.
  • Bell BD, Leverrier S, Weist BM, Newton RH, Arechiga AF, Luhrs KA, Morrissette NS, Walsh CM. FADD and caspase-8 control the outcome of autophagic signalling in proliferating T cells. PNAS. 2008;105:16677-82.
  • Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. 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;280:20722-9.
  • Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006;8:1124–32.
  • Cho DH, Jo YK, Hwang JJ, Lee YM, Roh SA, Kim JC: Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells. Cancer Lett 2009;274:95-100.
  • Wirawan E, Vandewalle L, Kersse K, et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis 2010;1-18.
  • Betin VM, Lane JD. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J Cell Sci 2009;122:2554-2566.
  • Walls KC, Ghosh AP, Franklin AV, et al. Lysosome dysfunction triggers Atg7-dependent neural apoptosis. J Biol Chem 2010; 285:10497-10507.
  • Radoshevich L, Murrow L, Chen N, et al. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 2010;142:590-600
  • Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene 2003;22:9030–40.
  • Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 2005;102:8204–9.
  • Tasdemir E, Maiuri M, Galluzzi L, Vitale I, Djavaheri-Mergny M, D’Amelio M,Criollo A, Morselli E, Zhu C, Harper F, Nannmark U, Samara C, Pinton P, Vicencio JM, Carnuccio R, Moll UM, Madeo F, Paterlini-Brechot P, Rizzuto R, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008;10:676–87.
  • Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 2007; 4:1749-60.
  • Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH, Lenardo M. Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci U S A 2006;28:4952-7.
  • Sherr CJ. The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol 2001;2:731–7.
  • Reef S, Shifman O, Oren M, Kimchi A. The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. Oncogene 2007;26:6677–83.
  • Yu L, Lenardo MJ, Baehrecke EH. Autophagy and caspases. Cell Cycle 2004;3:1124-6.
  • Lee JS, Li Q, Lee JY, et al. FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol 2009;11:1355-1362
  • Raveh T, Droguett G, Horwitz MS, DePinho RA, Kimchi A. DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nat Cell Biol 2001;3:1-7.
  • Jang CW, Chen CH, Chen CC, Chen JY, Su YH, Chen RH. TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Nat Cell Biol 2002;4:51-8.
  • Bialik S, Kimchi A. The death-associated protein kinases: structure, function and beyond. Annu Rev Biochem 2006;75:189–210 .
  • Harrison B, Kraus M, Burch L, Stevens C, Craig A, Gordon-Weeks P Hupp TR. DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and membrane blebbing. J Biol Chem 2008;283:9999–10014.
  • Halpain S, Dehmelt L. The MAP1 family of microtubule-associated proteins. Genome Biol 2006;7:224.
  • Stevens C, Lin Y, Harrison B, Burch L, Ridgway RA, Sansom O, Hupp T. Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling. J Biol Chem 2009;284:334-44.
  • Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M Sabanay H, Pinkas-Kramarski R, Kimchi A. DAPk-mediated phosphorylation on the BH3 domain of Beclin-1 promotes dissociation of Beclin-1 from Bcl-XL to induce autophagy. EMBO Rep 2009; 10: 285–92.
  • Gozuacik D, Bialik S, Raveh T, Mitou G, Shohat G, Sabanay H, Mizushima N, Yoshimori T, Kimchi A. DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death. Cell Death Differ. 2008;(12):1875-86.
  • Iaquinta P, Lees J. Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 2007;19:649–57.
  • Polager S, Ofir M, Ginsberg D. E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene 2008;27:4860–64.

Autophagy: a Cellular Stres and Cell Death Mechanism

Year 2011, Issue: 4, 184 - 194, 01.12.2011

Devrim Öz Arslan Gözde Korkmaz Devrim Gözüaçık

Abstract

Abstract: Autophagy is a physiological phenomenon responsible for the degradation of long-lived proteins, organelles and cytoplasmic fragments. It allows cellular recycling following lysosomal degradation and helps the cell to survive various stress conditions including starvation, growth factor and oxidative stress. Paradoxically, under certain conditions autophagy may kill the cell through a caspase-independent, non-apoptotic type of cell death Type II cell death or autophagic cell death . Several lines of evidence point out to a direct connection between classical apoptosis and autophagy. Molecular mechanisms of apoptosis-autophagy connection start to be unraveled. The cross-talk between autophagy and apoptosis seems quite complex but certainly is critical for the development of novel diagnosis, follow-up and treatment modalities in health problems such as cancer, infections and neurodegenerative diseases

Keywords

autophagy apoptosis cell survival signal tranduction

References

  • Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol 2001;2:211-6.
  • Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science 2004;306:990-5.
  • Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-75.
  • Yang Z, Klionsky D. Eaten alive: a history of macroautophagy. Nat Cell Biol 2010;12:814-822.
  • Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptaion. Nat Cell Biol 2007;9:1102-9.
  • Kroemer G, Marino G, Levine B. Autophagy and integrated stress response. Mol Cell 2010;40(2):280-293.
  • Mehrpour M, Esclatine A, Beau I, Codogno P. Overwiew of macroautophagy regulation in mammalian cells. Cell Research 2010;20:748-762.
  • Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 2000; 150:1507-13.
  • Shang L, Wang X. AMPK and mTOR coordinate the regulation of Ulk1 and mammalian autophagy initiation. Autophagy 2011;7(8):924-6.
  • Scott RC, Schuldiner O, Neufeld TP. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell 2004;7:167-8.
  • Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature 2001;411:355-65.
  • Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 2004;36:2445-62.
  • Ari co S, Petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P, Ogier-Denis E. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 2001; 276:35243-6.
  • Lia ng XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402:672-6.
  • Pfisterer SG, Mauthe M, Codogno P, Proikas-Cezanne T. Ca2+/Calmodulin-dependent kinase signaling via CaMKI and AMPK contributes to the regulation of WIPI-1 at the onset of autophagy. Molecular Pharmacology September 6, 2011 doi:10.1124/mol.111.071761
  • Ogi er-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, Isidoro C, Laburthe M, Codogno P. A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29. J Biol Chem 1995;270:13-16.
  • Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol 2002;157:455-8.
  • chromosomal instability. Genes Dev 2007;21:1367–81.
  • Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan R. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 2007;128:931-46.
  • Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M. Autophagy is involved in T cell death after binding of HIV envelope proteins to CXCR4. J Clin Invest 2006;116: 2161.
  • Corradetti M, Guan K. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 2006;25:6347–60.
  • Guertin D, Sabatini D. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9–22.
  • Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 2005;9:59–71.
  • McCubrey J, Steelman L, Chap pell W, Abrams S, Wong E, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007;1773:1263–84.
  • Ballif B, Blenis J. Molecular m echanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPk survival signals. Cell Growth Diff 2001;12: 397–408.
  • Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008;4:600-6.
  • Noble C, Dong J, Manser E, Song H. BCL-XL and UVRAG cause a monomer-dimer switch in beclin1. J Biol Chem 2008;283:26274–82.
  • Mellor HR, Harris AL. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. Cancer Metastasis Rev 2007;26:553-66.
  • Bell BD, Leverrier S, Weist BM, Newton RH, Arechiga AF, Luhrs KA, Morrissette NS, Walsh CM. FADD and caspase-8 control the outcome of autophagic signalling in proliferating T cells. PNAS. 2008;105:16677-82.
  • Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. 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;280:20722-9.
  • Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006;8:1124–32.
  • Cho DH, Jo YK, Hwang JJ, Lee YM, Roh SA, Kim JC: Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells. Cancer Lett 2009;274:95-100.
  • Wirawan E, Vandewalle L, Kersse K, et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis 2010;1-18.
  • Betin VM, Lane JD. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J Cell Sci 2009;122:2554-2566.
  • Walls KC, Ghosh AP, Franklin AV, et al. Lysosome dysfunction triggers Atg7-dependent neural apoptosis. J Biol Chem 2010; 285:10497-10507.
  • Radoshevich L, Murrow L, Chen N, et al. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 2010;142:590-600
  • Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene 2003;22:9030–40.
  • Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 2005;102:8204–9.
  • Tasdemir E, Maiuri M, Galluzzi L, Vitale I, Djavaheri-Mergny M, D’Amelio M,Criollo A, Morselli E, Zhu C, Harper F, Nannmark U, Samara C, Pinton P, Vicencio JM, Carnuccio R, Moll UM, Madeo F, Paterlini-Brechot P, Rizzuto R, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008;10:676–87.
  • Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 2007; 4:1749-60.
  • Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH, Lenardo M. Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci U S A 2006;28:4952-7.
  • Sherr CJ. The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol 2001;2:731–7.
  • Reef S, Shifman O, Oren M, Kimchi A. The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. Oncogene 2007;26:6677–83.
  • Yu L, Lenardo MJ, Baehrecke EH. Autophagy and caspases. Cell Cycle 2004;3:1124-6.
  • Lee JS, Li Q, Lee JY, et al. FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol 2009;11:1355-1362
  • Raveh T, Droguett G, Horwitz MS, DePinho RA, Kimchi A. DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nat Cell Biol 2001;3:1-7.
  • Jang CW, Chen CH, Chen CC, Chen JY, Su YH, Chen RH. TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Nat Cell Biol 2002;4:51-8.
  • Bialik S, Kimchi A. The death-associated protein kinases: structure, function and beyond. Annu Rev Biochem 2006;75:189–210 .
  • Harrison B, Kraus M, Burch L, Stevens C, Craig A, Gordon-Weeks P Hupp TR. DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and membrane blebbing. J Biol Chem 2008;283:9999–10014.
  • Halpain S, Dehmelt L. The MAP1 family of microtubule-associated proteins. Genome Biol 2006;7:224.
  • Stevens C, Lin Y, Harrison B, Burch L, Ridgway RA, Sansom O, Hupp T. Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling. J Biol Chem 2009;284:334-44.
  • Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M Sabanay H, Pinkas-Kramarski R, Kimchi A. DAPk-mediated phosphorylation on the BH3 domain of Beclin-1 promotes dissociation of Beclin-1 from Bcl-XL to induce autophagy. EMBO Rep 2009; 10: 285–92.
  • Gozuacik D, Bialik S, Raveh T, Mitou G, Shohat G, Sabanay H, Mizushima N, Yoshimori T, Kimchi A. DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death. Cell Death Differ. 2008;(12):1875-86.
  • Iaquinta P, Lees J. Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 2007;19:649–57.
  • Polager S, Ofir M, Ginsberg D. E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene 2008;27:4860–64.
There are 55 citations in total.

Details

Primary Language Turkish
Journal Section Collection
Authors

Devrim Öz Arslan

Gözde Korkmaz

Devrim Gözüaçık

Publication Date December 1, 2011
Published in Issue Year 2011Issue: 4

Cite

EndNote Arslan DÖ, Korkmaz G, Gözüaçık D (December 1, 2011) Otofaji: Bir Hücresel Stres Yanıtı ve Ölüm Mekanizması. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 4 184–194.