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      세포사멸 조절에서 PI3K-PTEN-PKB/Akt 신호전달계의 역할 = Regulation of Apoptosis by PI3K-PTEN-PKB/Akt Signaling Pathway

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      https://www.riss.kr/link?id=A104744722

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      다국어 초록 (Multilingual Abstract)

      Recently, the understanding of protein kinase B (PKB) activation and mechanisms for promoting cell survival has expanded rapidly. Several PKB substrates involved in apoptopsis have been described and many processes inhibiting cell death have been identified. In this context, the mitochondrion appears to be the key organelle in which PKB drives its anti-apoptotic activities. Additionally, by modulating transcription factor activity or inhibiting nucleus condensation/fragmentation, PKB interferes with upstream mitochondrial cell death signals, but it also maintains mitochondrial integrity by reinforcing the roles of key players acting on mitochondrial membranes. Moreover, caspase activity, which represents mitochondrial downstream events in the apoptotic process, can be prevented by PKB in different ways. More recent several studies have shown that mitochondria can also be fragmented in cells that normally undergo programmed cell death, supporting the notion that mitochondrial remodelling plays an important role in the process. The function of PKB is still not clear and further investigations of its possible role as a modulator of mitochondrial dynamics are required. This could lead to a major breakthrough in our understanding of PKB functions in cell survival and to the generation of powerful tools for cancer therapy. (Cancer Prev Res 13, 153-161, 2008)
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      Recently, the understanding of protein kinase B (PKB) activation and mechanisms for promoting cell survival has expanded rapidly. Several PKB substrates involved in apoptopsis have been described and many processes inhibiting cell death have been iden...

      Recently, the understanding of protein kinase B (PKB) activation and mechanisms for promoting cell survival has expanded rapidly. Several PKB substrates involved in apoptopsis have been described and many processes inhibiting cell death have been identified. In this context, the mitochondrion appears to be the key organelle in which PKB drives its anti-apoptotic activities. Additionally, by modulating transcription factor activity or inhibiting nucleus condensation/fragmentation, PKB interferes with upstream mitochondrial cell death signals, but it also maintains mitochondrial integrity by reinforcing the roles of key players acting on mitochondrial membranes. Moreover, caspase activity, which represents mitochondrial downstream events in the apoptotic process, can be prevented by PKB in different ways. More recent several studies have shown that mitochondria can also be fragmented in cells that normally undergo programmed cell death, supporting the notion that mitochondrial remodelling plays an important role in the process. The function of PKB is still not clear and further investigations of its possible role as a modulator of mitochondrial dynamics are required. This could lead to a major breakthrough in our understanding of PKB functions in cell survival and to the generation of powerful tools for cancer therapy. (Cancer Prev Res 13, 153-161, 2008)

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      참고문헌 (Reference)

      1 Lauder, A., "c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of T cells and is required for PKB-mediated protection from apoptosis" 21 : 5797-5805, 2001

      2 Ohba, N., "Transgenic mouse overexpressing the Akt reduced the volume of infarct area after middle cerebral artery occlusion" 359 : 159-162, 2004

      3 Kluck, R.M., "The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis" 275 : 1132-1136, 1997

      4 Yamaguchi, H., "The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change" 20 : 7779-7786, 2001

      5 Cantley, L.C., "The phosphoinositide 3-kinase pathway" 296 : 1655-1657, 2002

      6 Vivanco, I., "The phosphatidylinositol 3-Kinase AKT pathway in human cancer" 2 : 489-501, 2002

      7 Coutts, A.S., "The p53 response during DNA damage: impact of transcriptional cofactors" 181-189, 2006

      8 Wang, J.M., "The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB" 19 : 6195-6206, 1999

      9 Carracedo, A., "The PTEN-PI3K pathway: of feedbacks and cross-talks" 18 : 5527-5541, 2008

      10 Kennedy, S.G., "The PI3-kinase/Akt signaling pathway delivers an anti-apoptotic signal" 11 : 701-713, 1997

      1 Lauder, A., "c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of T cells and is required for PKB-mediated protection from apoptosis" 21 : 5797-5805, 2001

      2 Ohba, N., "Transgenic mouse overexpressing the Akt reduced the volume of infarct area after middle cerebral artery occlusion" 359 : 159-162, 2004

      3 Kluck, R.M., "The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis" 275 : 1132-1136, 1997

      4 Yamaguchi, H., "The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change" 20 : 7779-7786, 2001

      5 Cantley, L.C., "The phosphoinositide 3-kinase pathway" 296 : 1655-1657, 2002

      6 Vivanco, I., "The phosphatidylinositol 3-Kinase AKT pathway in human cancer" 2 : 489-501, 2002

      7 Coutts, A.S., "The p53 response during DNA damage: impact of transcriptional cofactors" 181-189, 2006

      8 Wang, J.M., "The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB" 19 : 6195-6206, 1999

      9 Carracedo, A., "The PTEN-PI3K pathway: of feedbacks and cross-talks" 18 : 5527-5541, 2008

      10 Kennedy, S.G., "The PI3-kinase/Akt signaling pathway delivers an anti-apoptotic signal" 11 : 701-713, 1997

      11 Feng, J., "Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation" 279 : 35510-35517, 2004

      12 Du, C., "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition" 102 : 33-42, 2000

      13 Pap, M., "Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway" 273 : 19929-19932, 1998

      14 Hu, Y., "Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis" 18 : 3586-3595, 1999

      15 Robertson, J.D., "Review: nuclear events in apoptosis" 129 : 346-358, 2000

      16 Cardone, M.H., "Regulation of cell death protease caspase-9 by phosphorylation" 282 : 1318-1321, 1998

      17 Liu, X., "Quantitative analysis of anti-apoptotic function of Akt in Akt1 and Akt2 double knock-out mouse embryonic fibroblast cells under normal and stressed conditions" 281 : 31380-31388, 2006

      18 Fayard, E., "Protein kinase B/Akt at a glance" 118 : 5675-5678, 2005

      19 Wymann, M.P., "Phosphoinositide 3-kinase signalling-which way to target?" 24 : 366-376, 2003

      20 Kim, N.H., "PKB/Akt inhibits ceramide-induced apoptosis in neuroblastoma cells by blocking apoptosis-inducing factor (AIF) translocation" 102 : 1160-1170, 2007

      21 Parcellier, A., "PKB and the mitochondria: AKTing on apoptosis" 20 : 21-30, 2008

      22 Yang, Q.H., "Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis" 17 : 1487-1496, 2003

      23 Ahn, J.Y., "Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase" 25 : 2083-2095, 2006

      24 Xin, M., "Nicotine inactivation of the proapoptotic function of Bax through phosphorylation" 280 : 10781-10789, 2005

      25 Ozes, O.N., "NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase" 401 : 82-85, 1999

      26 Gogvadze, V., "Multiple pathways of cytochrome c release from mitochondria in apoptosis" 1757 : 639-647, 2006

      27 Goldenthal, M.J., "Mitochondrial signaling pathways: a receiver/integrator organelle" 262 : 1-16, 2004

      28 McQuibban, G.A., "Mitochondrial membrane remodelling regulated by a conserved rhomboid protease" 423 : 537-541, 2003

      29 Yu, S.W., "Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor" 297 : 259-263, 2002

      30 Schwertfeger, K.L., "Mammary gland involution is delayed by activated Akt in transgenic mice" 15 : 867-881, 2001

      31 del Peso, L., "Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt" 278 : 687-689, 1997

      32 Solit, D.B., "Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol" 63 : 2139-2144, 2003

      33 Cross, D.A., "Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B" 378 : 785-789, 1995

      34 Gottlob, K., "Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase" 15 : 1406-1418, 2001

      35 Reusch, J.E., "Inhibition of cAMP-response element- binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and induces apoptosis" 277 : 1426-1432, 2002

      36 Bryson, J.M., "Increased hexokinase activity, of either ectopic or endogenous origin, protects renal epithelial cells against acute oxidant-induced cell death" 277 : 11392-11400, 2002

      37 Wu, R., "Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex" 282 : 21598-21608, 2007

      38 Wilson, J.E., "Hexokinases" 126 : 65-198, 1995

      39 Majewski, N., "Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak" 16 : 819-830, 2004

      40 Maurer, U., "Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1" 21 : 749-760, 2006

      41 Petit, P.X., "Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition" 426 : 111-116, 1998

      42 Kops, G.J., "Direct control of the Forkhead transcription factor AFX by protein kinase B" 398 : 630-634, 1999

      43 Burgering, B.M., "Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty" 73 : 689-701, 2003

      44 Oren, M., "Decision making by p53: life, death and cancer" 10 : 431-442, 2003

      45 Ott, M., "Cytochrome c release from mitochondria proceeds by a two-step process" 1259-1263, 2002

      46 Dutta, J., "Current insights into the regulation of programmed cell death by NF-κB" 25 : 6800-6816, 2006

      47 Spierings, D., "Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis" 310 : 66-67, 2005

      48 Nechushtan, A., "Conformation of the Bax C-terminus regulates subcellular location and cell death" 18 : 2330-2341, 1999

      49 Tsujimoto, Y., "Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation" 226 : 1097-1099, 1984

      50 Stoica, B.A., "Ceramide- induced neuronal apoptosis is associated with dephosphorylation of Akt, BAD, FKHR, GSK-3β, and induction of the mitochondrial-dependent intrinsic caspase pathway" 22 : 365-382, 2003

      51 Datta, S.R., "Cellular survival: a play in three Akts" 13 : 2905-2927, 1999

      52 Cully, M., "Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis" 6 : 184-192, 2006

      53 Vaux, D.L., "Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells" 335 : 440-442, 1988

      54 Candé, C., "Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?" 115 : 4727-4734, 2002

      55 Zou, H., "An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9" 274 : 11549-11556, 1999

      56 Sugatani, T., "Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors" 280 : 3583-3589, 2005

      57 Pugazhenthi, S., "Akt/protein kinase B up- regulates Bcl-2 expression through cAMP-response element- binding protein" 275 : 10761-10766, 2000

      58 Kennedy, S.G., "Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria" 19 : 5800-5810, 1999

      59 Rathmell, J.C., "Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival" 23 : 7315-7328, 2003

      60 Kim, A.H., "Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1" 21 : 893-901, 2001

      61 Yang, L., "Akt attenuation of the serine protease activity of HtrA2/Omi through phosphorylation of serine 212" 282 : 10981-10987, 2007

      62 Park, H.S., "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation" 277 : 2573-2578, 2002

      63 Brazil, D.P., "Advances in protein kinase B signalling: AKTion on multiple fronts" 29 : 233-242, 2004

      64 Konishi, H., "Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27" 410 : 493-498, 1997

      65 Sahara, S., "Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation" 401 : 168-173, 1999

      66 Suzuki, Y., "A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death" 8 : 613-621, 2001

      67 Enari, M., "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD" 391 : 43-50, 1998

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      연월일 이력구분 이력상세 등재구분
      2022 평가예정 재인증평가 신청대상 (재인증)
      2019-01-01 평가 등재학술지 선정 (계속평가) KCI등재
      2018-12-01 평가 등재후보로 하락 (계속평가) KCI등재후보
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2013-10-14 학술지명변경 외국어명 : Cancer Prevention Research -> Journal of Cancer Prevention KCI등재
      2012-10-15 학회명변경 영문명 : Korean Association of Cancer Prevention -> Korean Society of Cancer Preveniton KCI등재
      2011-04-04 학술지명변경 외국어명 : Journal of Korean Association of Cancer Prevention -> Cancer Prevention Research KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2008-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2007-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2005-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      2016 0.22 0.22 0.18
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.15 0.12 0.405 0.13
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