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浙江大学学报(医学版)  2013, Vol. 42 Issue (2): 217-223    DOI: 10.3785/j.issn.1008-9292.2013.02.014
综述     
p53非依赖性信号通路在DNA损伤致细胞凋亡中的研究进展
张潇芸1,姜英2,杨军1,3
1.浙江大学公共卫生院毒理学系,浙江 杭州 310058;
2.深圳华测检测技术股份有限公司,广州 深圳 518101;
3.杭州师范大学公共卫生学院,浙江 杭州 310036;
p53-independent signaling pathway in DNA damage-induced cell apoptosis
ZHANG Xiao-Yun1, JIANG Ying2, YANG Jun1,3
1.Zhejiang University School of Public Health,Hangzhou 310058,China;2.Center Testing International Corporation,Guangdong 518101,China;3.Department of Toxicology,Hangzhou Normal University School of Public Health,Hangzhou 310036,China;
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摘要:

p53在DNA损伤诱导细胞凋亡中发挥关键作用,但p53基因在大多数肿瘤细胞中易发生突变,突变率可超过50%。目前研究发现,p73、p63、Caspase 2、NF-κB等蛋白介导的信号通路能够在p53非依赖的DNA损伤诱导细胞凋亡中发挥作用。因此,有必要对p53非依赖信号通路近年来的研究进展作一综述,为癌症治疗提供新的思路。

关键词: DNA损伤基因p53信号传导p53细胞凋亡p53非依赖信号通路    
Abstract:

p53 is considered as the “master regulator” in DNA damage-induced cell apoptosis.However,p53 is the most frequently mutated gene in human cancers (more than 50%).Thus the research of p53-independent pathway in cell apoptosis may ultimately provide new therapeutic opportunities for many cancers.It has been shown that Caspase 2,p73,p63,and NF-κB-related signaling pathways are involved in DNA damage-induced,p53-independent cell apoptosis.This article reviews the recent research progress in these signaling pathways.

Key words: DNA damage    Genes,p53    Signal transduction    p53    cell apoptosis    p53-independent pathway
收稿日期: 2012-03-22 出版日期: 2013-03-25
:  R 730.2  
基金资助:

国家自然科学基金资助项目(81173692和81202241);浙江省自然科学基金资助项目(R2100555);中国博士后科学基金资助项目(2011M501020).

通讯作者: 杨军(1969-),男,博士,教授,从事分子毒理学研究     E-mail: gastate@zju.edu.cn
作者简介: 张潇芸(1986-),女,硕士研究生.
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引用本文:

张潇芸, 姜英, 杨军. p53非依赖性信号通路在DNA损伤致细胞凋亡中的研究进展[J]. 浙江大学学报(医学版), 2013, 42(2): 217-223.

ZHANG Xiao-Yun, JIANG Ying, YANG Jun. p53-independent signaling pathway in DNA damage-induced cell apoptosis. Journal of ZheJiang University(Medical Science), 2013, 42(2): 217-223.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2013.02.014        http://www.zjujournals.com/med/CN/Y2013/V42/I2/217

 


[1]YU Q.Restoring p53-mediated apoptosis in cancer cells:new opportunities for cancer therapy
[J]. Drug Resist Update,2006,9(1-2):19-25.

[2]LU J,MOOCHHALA S,KAUR C,et al.Changes in apoptosis-related protein (p53,Bax,Bcl-2 and Fos) expression with DNA fragmentation in the central nervous system in rats after closed head injury
[J]. Neurosci Lett,2000,290(2):89-92.

[3]INAMURA N,ARAKI T,ENOKIDO Y,et al.Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum
[J]. J Neurosci Res,2000,60(4):450-457.

[4]LACKINGER D,EICHHORN U,KAINA B,et al.Effect of ultraviolet light,methyl methanesulfonate and ionizing radiation on the genotoxic response and apoptosis of mouse fibroblasts lacking c-Fos,p53 or both
[J]. Mutagenesis,2001,16(3):233-241.

[5]LIPS J,KAINA B.DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts
[J]. Carcinogenesis,2001,22(4):579-585.

[6]TALUKDER K A,AZMI I J,AHMED K A,et al.Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells
[J]. Microb Pathog,2012,In Press,PMID:22406215.

[7]ROOS W P,KAINA B.DNA damage-induced apoptosis:From specific DNA lesions to the DNA damage response and apoptosis
[J]. Cancer Lett,2012,In Press,PMID:22261329.5

[8]BORGES H L,LINDEN R,WANG J Y,et al.DNA damage-induced cell death:lessons from the central nervous system
[J]. Cell Res,2008,18(1):17-26.

[9]DEYOUNG M P,ELLISEN L W.p63 and p73 in human cancer:defining the network
[J]. Oncogene,2007,26(36):5169-5183.

[10]LEONG C O,VIDNOVIC N,DEYOUNG M P,et al.The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers
[J]. J Clin Invest,2007,117(5):1370-1380.

[11]ALLOCATI N,ILIO C D,LAURENZI V D,et al.p63/p73 in the control of cell cycle and cell death
[J]. Experimental Cell Research,2012,In Press,PMID:22326462.

[12]BARBIERI C E,TANG L J,BROWN K A,et al.Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis
[J]. Cancer Research,2006,66(15):7589-7597.

[13]BUHLMANN S,PUTZER B M.DNp73 a matter of cancer:mechanisms and clinical implications
[J]. Biochim Biophys Acta,2008,1785(2):207-216.

[14]HELTON E S,ZHU J,CHEN X,et al.The unique NH2-terminally deleted (DeltaN) residues,the PXXP motif,and the PPXY motif are required for the transcriptional activity of the DeltaN variant of p63
[J]. Journal of Biological Chemistry,2006,281(5):2533-2542.

[15]DEYOUNG M P,JOHANNESSEN C M,LEONG C O,et al.Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma
[J]. Cancer Research,2006,66(19):9362-9368.

[16]MAAS A M,BRETZ A C,MACK E,et al.Targeting p73 in cancer
[J]. Cancer Lett,2011,In Press,PMID: 21903324.

[17]FLORES E R,SENGUPTA S,MILLER J B,et al.Tumor predisposition in mice mutant for p63 and p73:evidence for broader tumor suppressor functions for the p53 family
[J]. Cancer Cell,2005,7(4):363-373.

[18]DAI J M,WANG Z Y,SUN D C,et al.SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity
[J]. J Cell Physiol,2007,210(1):161-166.

[19]DIETZ S,ROTHER K,BAMBERGER C,et al.Differential regulation of transcription and induction of programmed cell death by human p53-family members p63 and p73
[J]. Febs Letters,2002,525(1-3):93-99.

[20]ROOS W P,KAINA B.DNA damage-induced cell death by apoptosis
[J]. Trends in Molecular Medicine,2006,12(9):440-450.

[21]YOSHIDA K,OZAKI T,FURUYA K,et al.ATM-dependent nuclear accumulation of IKK-alpha plays an important role in the regulation of p73-mediated apoptosis in response to cisplatin
[J]. Oncogene,2008,27(8):1183-1188.

[22]FLINTERMAN M,GUELEN L,EZZATI-NIK S,et al.E1A activates transcription of p73 and Noxa to induce apoptosis
[J]. Journal of Biological Chemistry,2005,280(7):5945-5959.

[23]BAPTISTE-OKOH N,BARSOTTI A M,PRIVES V,et al.A role for caspase 2 and PIDD in the process of p53-mediated apoptosis
[J]. Proc Natl Acad Sci USA,2008,105(6):1937-1942.

[24]MANZL C,KRUMSCHNABEL G,BOCK F,et al.Caspase-2 activation in the absence of PIDDosome formation
[J]. Journal of Cell Biology,2009,185(2):291-303.

[25]SAMRAJ A K,SOHN D,SCHULZE-OSTHOFF K,et al.Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization
[J]. Mol Biol Cell,2007,18(1):84-93.

[26]LASSUS P,OPITZ-ARAYA X,Lazebnik Y,et al.Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization
[J]. Science,2002,297(5585):1352-1354.

[27]NORBERG H,ZHIVOTOSKY B.The unpredictable caspase-2:what can it do
[J]?Trends Cell Biol,2010,20(3):150-159.

[28]DOLCET X,LIOBET D,PALLARES J,et al.NF-kB in development and progression of human cancer
[J]. Virchows Arch,2005,446(5):475-482.

[29]SARIS N E,CARAFOLI E.A historical review of cellular calcium handling,with emphasis on mitochondria
[J]. Biochemistry (Mosc),2005,70(2):187-194.

[30]MUER A,OVERKAMP T,GILLISSEN B,et al.p14ARF-induced apoptosis in p53-deficient cells is mediated by the BH3-only protein independent de-repression of Bak through down-regulation of Mcl-1 and Bcl-xL
[J]. Journal of Biological Chemistry,2012,InPress,PMID:22354970.

[31]YUAN X W,ZHU X F,HUANG X F,et al.P14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner
[J]. Cancer Biology & Therapy,2007,6(7):1074-1080.

[32]ZHANG H J,LI W J,GU Y Y,et al.p14ARF interacts with E2F factors to form p14ARF-E2F/partner-DNA complexes repressing E2F-dependent transcription
[J]. J Cell Biochem,2010,109(4):693-701.

[33]HU G,MANCL M E,BAMES B J,et al.Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA damage-induced apoptosis and cell death
[J]. Cancer Research,2005,65(16):7403-7412.

[34]HAYNES T A,DUERKSEN P J,FILIPPOVA M,et al.C18 ceramide analysis in mammalian cells employing reversed-phase high-performance liquid chromatography tandem mass spectrometry
[J]. Anal Biochem,2008,378(1):80-86.

[35]HAYNES T A,FILIPPOV V,FILIPPOV M,et al.DNA damage induces down-regulation of UDP-glucose ceramide glucosyltransferase,increases ceramide levels and triggers apoptosis in p53-deficient cancer cells
[J]. Biochim Biophys Acta,2012,InPress,PMID:22354970.

[36]ELMORE S.Apoptosis:a review of programmed cell death
[J]. Toxicologic Pathology,2007,35(4):495-516.

[37]MCNAMEE L M,BRODSKY M H.p53-independent apoptosis limits DNA damage-induced aneuploidy
[J]. Genetics,2009,182(2):423-435.

[38]DHANASEKARAN D N,KASHEF K,LEE C M,et al.Scaffold proteins of MAP-kinase modules
[J].Oncogene,2007,26(22):3185-3202.
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