title: Mouse models of p53 functions.
abstract: Studies in mice have yielded invaluable insight into our understanding of the p53 pathway. Mouse models with activated p53, no p53, and mutant p53 have queried the role of p53 in development and tumorigenesis. In these models, p53 is activated and stabilized via redundant posttranslational modifications. On activation, p53 initiates two major responses: inhibition of proliferation (via cell-cycle arrest, quiescence, senescence, and differentiation) and induction of apoptosis. Importantly, these responses are cell-type and tumor-type-specific. The analysis of mutant p53 alleles has established a gain-of-function role for p53 mutants in metastasis. The development of additional models that can precisely time the oncogenic events in single cells will provide further insight into the evolution of tumors, the importance of the stroma, and the cooperating events that lead to disruption of the p53 pathway. Ultimately, these models should serve to study the effects of novel drugs on tumor response as well as normal homeostasis.
authors.affiliation: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA. gglozano@mdanderson.org <gglozano@mdanderson.org>
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53
references.citation: Nature. 1992 Mar 19;356(6366):215-21
references.pmid: 1552940
references.citation: Nature. 2006 Sep 14;443(7108):214-7
references.pmid: 16957739
references.citation: Cell Death Differ. 2008 Nov;15(11):1772-81
references.pmid: 18636077
references.citation: EMBO J. 2003 Mar 17;22(6):1442-50
references.pmid: 12628936
references.citation: Nat Genet. 2001 Sep;29(1):92-5
references.pmid: 11528400
references.citation: Cell. 2004 Dec 17;119(6):847-60
references.pmid: 15607980
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2834-7
references.pmid: 9501176
references.citation: Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001081
references.pmid: 20457560
references.citation: EMBO J. 1996 Feb 15;15(4):827-38
references.pmid: 8631304
references.citation: J Cell Biol. 2006 Jan 2;172(1):115-25
references.pmid: 16380437
references.citation: Differentiation. 2009 Jun;77(5):442-9
references.pmid: 19371999
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6399-402
references.pmid: 9600977
references.citation: Nature. 2007 Feb 8;445(7128):661-5
references.pmid: 17251932
references.citation: Cancer Res. 2007 Dec 15;67(24):11696-703
references.pmid: 18089799
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3232-7
references.pmid: 16492744
references.citation: Cancer Cell. 2002 Aug;2(2):103-12
references.pmid: 12204530
references.citation: Oncogene. 2008 Mar 6;27(11):1590-8
references.pmid: 17828300
references.citation: J Neurosci. 2001 Sep 1;21(17):6687-93
references.pmid: 11517258
references.citation: Mol Cell Biol. 2004 Feb;24(3):976-84
references.pmid: 14729946
references.citation: Mol Cell Biol. 2006 Jan;26(1):192-8
references.pmid: 16354690
references.citation: Hum Pathol. 2007 Oct;38(10):1553-62
references.pmid: 17651783
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10188-93
references.pmid: 16006521
references.citation: J Pathol. 2005 Jan;205(2):206-20
references.pmid: 15643668
references.citation: Nat Genet. 1993 Nov;5(3):225-9
references.pmid: 8275085
references.citation: Mol Cell Biol. 1996 Sep;16(9):4952-60
references.pmid: 8756654
references.citation: Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a000968
references.pmid: 20182601
references.citation: Oncogene. 2007 Apr 2;26(15):2177-84
references.pmid: 17401426
references.citation: Nature. 1995 Nov 9;378(6553):203-6
references.pmid: 7477326
references.citation: Mol Cell Biol. 2002 Aug;22(15):5527-38
references.pmid: 12101245
references.citation: PLoS One. 2008;3(11):e3707
references.pmid: 19002260
references.citation: Nature. 2008 Oct 23;455(7216):1129-33
references.pmid: 18948956
references.citation: EMBO J. 1998 Aug 17;17(16):4657-67
references.pmid: 9707425
references.citation: Semin Cancer Biol. 1998;8(5):337-44
references.pmid: 10101799
references.citation: Nat Genet. 1994 Sep;8(1):66-9
references.pmid: 7987394
references.citation: Cell. 1994 Aug 26;78(4):703-11
references.pmid: 8069917
references.citation: Nature. 1995 Nov 9;378(6553):206-8
references.pmid: 7477327
references.citation: Circulation. 2007 Jun 12;115(23):2925-30
references.pmid: 17533180
references.citation: Cell Stem Cell. 2009 Jan 9;4(1):37-48
references.pmid: 19128791
references.citation: Curr Biol. 1995 Aug 1;5(8):931-6
references.pmid: 7583151
references.citation: Nature. 1993 Apr 29;362(6423):847-9
references.pmid: 8479522
references.citation: Nature. 1993 Apr 29;362(6423):849-52
references.pmid: 8479523
references.citation: Cell. 2008 Feb 22;132(4):631-44
references.pmid: 18295580
references.citation: Exp Cell Res. 1994 Mar;211(1):90-8
references.pmid: 8125163
references.citation: Nat Rev Cancer. 2001 Nov;1(2):157-62
references.pmid: 11905807
references.citation: Cancer Res. 1994 Feb 1;54(3):614-7
references.pmid: 8306319
references.citation: Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001107
references.pmid: 20182618
references.citation: Oncogene. 2007 Feb 26;26(9):1306-16
references.pmid: 17322916
references.citation: Genes Dev. 2006 Jan 1;20(1):16-21
references.pmid: 16391230
references.citation: Eur J Biochem. 2001 May;268(10):2764-72
references.pmid: 11358490
references.citation: Blood. 2007 Mar 15;109(6):2630-3
references.pmid: 17105817
references.citation: EMBO J. 2004 Sep 15;23(18):3689-99
references.pmid: 15343266
references.citation: Mol Cell Biol. 2007 Aug;27(15):5479-85
references.pmid: 17526734
references.citation: Nat Genet. 2004 Jan;36(1):63-8
references.pmid: 14702042
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19842-7
references.pmid: 17170138
references.citation: Cell. 1993 Nov 19;75(4):817-25
references.pmid: 8242752
references.citation: Genes Dev. 1994 Jun 1;8(11):1300-10
references.pmid: 7986270
references.citation: Nat Cell Biol. 2007 May;9(5):573-80
references.pmid: 17417627
references.citation: Nat Genet. 2005 Feb;37(2):145-52
references.pmid: 15654339
references.citation: Genes Dev. 2008 May 15;22(10):1337-44
references.pmid: 18483220
references.citation: Cell. 2004 Dec 17;119(6):861-72
references.pmid: 15607981
references.citation: Nat Genet. 2005 Jul;37(7):718-26
references.pmid: 15924142
references.citation: Cancer Cell. 2006 Dec;10(6):501-14
references.pmid: 17157790
references.citation: Cell Death Differ. 2006 Jun;13(6):927-34
references.pmid: 16543935
references.citation: Nat Rev Cancer. 2009 Nov;9(11):831-41
references.pmid: 19776746
references.citation: Mol Cell Biol. 2004 Oct;24(20):8884-94
references.pmid: 15456863
references.citation: Cell. 2002 May 3;109(3):335-46
references.pmid: 12015983
references.citation: Cell. 1993 Nov 19;75(4):805-16
references.pmid: 8242751
references.citation: Nature. 2007 Feb 8;445(7128):656-60
references.pmid: 17251933
references.citation: Cell. 2006 Dec 29;127(7):1323-34
references.pmid: 17182091
references.citation: EMBO J. 2006 Jun 7;25(11):2615-22
references.pmid: 16757976
references.citation: Nat Genet. 1995 Jun;10(2):175-80
references.pmid: 7663512
references.citation: Nature. 2007 Nov 29;450(7170):721-4
references.pmid: 18046411
references.citation: Cell Death Differ. 2006 Dec;13(12):2089-98
references.pmid: 16729027
references.citation: Exp Hematol. 2008 Oct;36(10):1236-43
references.pmid: 18562080
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3226-31
references.pmid: 16492743
references.citation: J Pathol. 2007 Dec;213(4):360-8
references.pmid: 17893884
references.citation: J Cell Biol. 2006 Mar 13;172(6):909-21
references.pmid: 16533949
references.citation: Curr Biol. 1994 Jan 1;4(1):1-7
references.pmid: 7922305
references.citation: Nat Rev Cancer. 2006 Dec;6(12):909-23
references.pmid: 17128209
references.citation: Oncogene. 1994 Jun;9(6):1767-73
references.pmid: 8183575
references.citation: Genes Dev. 1996 Apr 1;10(7):836-50
references.pmid: 8846920