p73和p63的治疗前景：从p53的阴影中崛起。
Therapeutic prospects for p73 and p63: rising from the shadow of p53.
作者信息
Vilgelm Anna, El-Rifai Wael, Zaika Alexander
机构信息
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
出版信息
Drug Resist Updat. 2008 Aug-Oct;11(4-5):152-63. doi: 10.1016/j.drup.2008.08.001. Epub 2008 Sep 17.
Abstract
The p53 protein family consists of three transcription factors: p53, p63, and p73. These proteins share significant structural and functional similarities and each has unique biological functions as well. Although the role of p53 in cellular stress is extensively studied, many questions remain about p63 and p73. In this review we summarize current data on functional interactions within the p53 family, their regulation and roles in response to genotoxic stress. We also discuss the significance of p73 and p63 for cancer therapy and outline novel approaches in development of therapeutic drugs that specifically target the p53 family.
摘要
p53蛋白家族由三种转录因子组成：p53、p63和p73。这些蛋白具有显著的结构和功能相似性，且各自也具有独特的生物学功能。尽管p53在细胞应激中的作用已得到广泛研究，但关于p63和p73仍存在许多问题。在本综述中，我们总结了p53家族内功能相互作用的当前数据，它们在响应基因毒性应激时的调节及作用。我们还讨论了p73和p63在癌症治疗中的意义，并概述了开发特异性靶向p53家族的治疗药物的新方法。
相似文献
1
Therapeutic prospects for p73 and p63: rising from the shadow of p53.p73和p63的治疗前景：从p53的阴影中崛起。
Drug Resist Updat. 2008 Aug-Oct;11(4-5):152-63. doi: 10.1016/j.drup.2008.08.001. Epub 2008 Sep 17.
2
p63 and p73: roles in development and tumor formation.p63和p73：在发育和肿瘤形成中的作用
Mol Cancer Res. 2004 Jul;2(7):371-86.
3
p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress.p53/p63/p73 异构体：协调细胞分化与应激反应的异构体“管弦乐队”
Cell Death Differ. 2006 Jun;13(6):962-72. doi: 10.1038/sj.cdd.4401914.
4
One billion years of p53/p63/p73 evolution.十亿年的p53/p63/p73进化历程。
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17609-10. doi: 10.1073/pnas.0910634106. Epub 2009 Oct 13.
5
The functional domains in p53 family proteins exhibit both common and distinct properties.p53家族蛋白中的功能域表现出共同和独特的特性。
Cell Death Differ. 2006 Jun;13(6):890-7. doi: 10.1038/sj.cdd.4401904.
6
Structural evolution of p53, p63, and p73: implication for heterotetramer formation.p53、p63和p73的结构演变：对异源四聚体形成的影响。
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17705-10. doi: 10.1073/pnas.0905867106. Epub 2009 Oct 7.
7
From p63 to p53 across p73.从p63经p73至p53。
FEBS Lett. 2001 Feb 16;490(3):163-70. doi: 10.1016/s0014-5793(01)02119-6.
8
The p53/p63/p73 family of transcription factors: overlapping and distinct functions.转录因子p53/p63/p73家族：重叠与独特的功能
J Cell Sci. 2000 May;113 ( Pt 10):1661-70. doi: 10.1242/jcs.113.10.1661.
9
Evolution of functions within the p53/p63/p73 family.p53/p63/p73家族内功能的演变。
Ann N Y Acad Sci. 2000;926:90-100. doi: 10.1111/j.1749-6632.2000.tb05602.x.
10
p73 and p63: why do we still need them?p73和p63：我们为何仍然需要它们？
Cell Cycle. 2004 Jul;3(7):886-94. Epub 2004 Jul 2.
引用本文的文献
1
Unlocking the Gateway: The Spatio-Temporal Dynamics of the p53 Family Driven by the Nuclear Pores and Its Implication for the Therapeutic Approach in Cancer.解锁门户：核孔驱动的 p53 家族的时空动力学及其对癌症治疗方法的启示。
Int J Mol Sci. 2024 Jul 7;25(13):7465. doi: 10.3390/ijms25137465.
2
Development of an integrated CRISPRi targeting ΔNp63 for treatment of squamous cell carcinoma.开发用于治疗鳞状细胞癌的靶向ΔNp63的整合型CRISPR干扰技术。
Oncotarget. 2018 Jun 26;9(49):29220-29232. doi: 10.18632/oncotarget.25678.
3
MDM2 Antagonists Counteract Drug-Induced DNA Damage.MDM2 拮抗剂对抗药物诱导的 DNA 损伤。
EBioMedicine. 2017 Oct;24:43-55. doi: 10.1016/j.ebiom.2017.09.016. Epub 2017 Sep 19.
4
Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade.洛伐他汀通过AMPK-p63-生存素信号级联反应导致下咽癌细胞FaDu死亡。
Sci Rep. 2016 Apr 28;6:25082. doi: 10.1038/srep25082.
5
The NAD(+) salvage pathway modulates cancer cell viability via p73.烟酰胺腺嘌呤二核苷酸（NAD(+)）补救途径通过p73调节癌细胞的活力。
Cell Death Differ. 2016 Apr;23(4):669-80. doi: 10.1038/cdd.2015.134. Epub 2015 Nov 20.
6
Role of the nucleus in apoptosis: signaling and execution.细胞核在细胞凋亡中的作用：信号传导与执行
Cell Mol Life Sci. 2015 Dec;72(23):4593-612. doi: 10.1007/s00018-015-2031-y. Epub 2015 Sep 7.
7
Progress in the identification of subgroups in ALK-negative anaplastic large-cell lymphoma.ALK阴性间变性大细胞淋巴瘤亚组鉴定的进展
Biomark Med. 2015;9(8):719-22. doi: 10.2217/BMM.15.37. Epub 2015 Jul 30.
8
p53 Family and Cellular Stress Responses in Cancer.癌症中的p53家族与细胞应激反应
Front Oncol. 2014 Oct 21;4:285. doi: 10.3389/fonc.2014.00285. eCollection 2014.
9
Somatic rearrangement of the TP63 gene preceding development of mycosis fungoides with aggressive clinical course.蕈样肉芽肿出现侵袭性临床病程之前TP63基因的体细胞重排。
Blood Cancer J. 2014 Oct 17;4(10):e253. doi: 10.1038/bcj.2014.73.
10
KPT-330 has antitumour activity against non-small cell lung cancer.KPT-330 对非小细胞肺癌具有抗肿瘤活性。
Br J Cancer. 2014 Jul 15;111(2):281-91. doi: 10.1038/bjc.2014.260. Epub 2014 Jun 19.
本文引用的文献
1
E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell lines.E2F-1转录活性是Mdm2拮抗剂诱导人肿瘤细胞系凋亡的关键决定因素。
Oncogene. 2008 Sep 11;27(40):5303-14. doi: 10.1038/onc.2008.164. Epub 2008 Jun 2.
2
Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway.小分子RETRA通过p73依赖的挽救途径抑制携带突变型p53的癌细胞。
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6302-7. doi: 10.1073/pnas.0802091105. Epub 2008 Apr 18.
3
Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage.c-Abl介导的Yap1磷酸化是细胞响应DNA损伤时选择性激活促凋亡基因的关键步骤。
Mol Cell. 2008 Feb 15;29(3):350-61. doi: 10.1016/j.molcel.2007.12.022.
4
Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73.ASPP蛋白的生化与结构研究揭示了其与p53、p63和p73的差异结合。
Structure. 2008 Feb;16(2):259-68. doi: 10.1016/j.str.2007.11.012.
5
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity.p53家族内的C末端多样性导致DNA结合和转录活性的差异。
Nucleic Acids Res. 2008 Apr;36(6):1900-12. doi: 10.1093/nar/gkn044. Epub 2008 Feb 11.
6
HtrA2 enhances the apoptotic functions of p73 on bax.HtrA2增强了p73对bax的凋亡功能。
Cell Death Differ. 2008 May;15(5):849-58. doi: 10.1038/cdd.2008.7. Epub 2008 Feb 8.
7
Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis through physical interaction and phosphorylation.Plk1通过物理相互作用和磷酸化在p73依赖性凋亡调控中的抑制作用。
J Biol Chem. 2008 Mar 28;283(13):8555-63. doi: 10.1074/jbc.M710608200. Epub 2008 Jan 3.
8
Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with DeltaNp73.p63六种同工型的特性：对基因毒性应激的p53样调控以及与DeltaNp73的相互作用。
Carcinogenesis. 2008 Feb;29(2):273-81. doi: 10.1093/carcin/bgm258. Epub 2007 Nov 28.
9
p73 expression modulates p63 and Mdm2 protein presence in complex with p53 family-specific DNA target sequence in squamous cell carcinogenesis.在鳞状细胞癌发生过程中，p73表达调节与p53家族特异性DNA靶序列结合的p63和Mdm2蛋白的存在。
Oncogene. 2008 Apr 24;27(19):2780-7. doi: 10.1038/sj.onc.1210941. Epub 2007 Nov 19.
10
DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function.DeltaNp73α 通过抑制 p53 功能来调节多药耐药基因 1（MDR1）的表达。
Oncogene. 2008 Apr 3;27(15):2170-6. doi: 10.1038/sj.onc.1210862. Epub 2007 Oct 22.
Zotero 插件