Posttranslational modification of p53: cooperative integrators of function.
The p53 protein is modified by as many as 50 individual posttranslational modifications. Many of these occur in response to genotoxic or nongenotoxic stresses and show interdependence, such that one or more modifications can nucleate subsequent events. This interdependent nature suggests a pathway that operates through multiple cooperative events as opposed to distinct functions for individual, isolated modifications. This concept, supported by recent investigations, which provide exquisite detail as to how various modifications mediate precise protein-protein interactions in a cooperative manner, may explain why knockin mice expressing p53 proteins substituted at one or just a few sites of modification typically show only subtle effects on p53 function. The present article focuses on recent, exciting progress and develops the idea that the impact of modification on p53 function is achieved through collective and integrated events.
Meek
David W
DW
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. d.w.meek@dundee.ac.uk
Anderson
Carl W
CW
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53
Mol Cell. 2004 Mar 26;13(6):867-78
15053879
J Biol Chem. 2002 Apr 12;277(15):12491-4
11875057
Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7009-14
17438265
Mol Cell Biol. 2000 Nov;20(22):8458-67
11046142
Cell Death Differ. 2007 Sep;14(9):1561-75
17627286
EMBO J. 1999 Dec 15;18(24):7002-10
10601022
J Biol Chem. 2000 Mar 31;275(13):9278-83
10734067
Mol Cell Biol. 1988 Jan;8(1):461-5
2827007
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13777-82
10570149
J Exp Med. 2006 Dec 25;203(13):2793-9
17158963
FEBS Lett. 2005 Sep 12;579(22):5007-12
16122737
Histol Histopathol. 2008 Sep;23(9):1143-9
18581285
Cancer Res. 2007 Dec 15;67(24):11696-703
18089799
Nature. 2004 Mar 25;428(6981):431-7
15042092
Mol Cell Biol. 2004 Feb;24(3):976-84
14729946
Nature. 2007 Sep 6;449(7158):105-8
17805299
J Biol Chem. 1995 Oct 20;270(42):25014-9
7559631
Cell. 1992 Nov 27;71(5):875-86
1423635
Genes Dev. 1998 Aug 1;12(15):2434-42
9694807
J Biol Chem. 2007 Jan 19;282(3):1797-804
17098746
Mol Cell. 2006 Dec 28;24(6):827-39
17189186
EMBO J. 1999 Nov 15;18(22):6455-61
10562557
Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10188-93
16006521
Mol Cell. 2006 Jun 23;22(6):731-740
16793543
Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11
1933891
Mech Dev. 2008 Nov-Dec;125(11-12):919-31
18835440
Mol Cell Biol. 1992 Nov;12(11):5041-9
1406679
Oncogene. 2007 Apr 2;26(15):2177-84
17401426
J Mol Biol. 2009 May 15;388(4):691-702
19303885
Nature. 1995 Nov 9;378(6553):203-6
7477326
Nat Rev Cancer. 2009 Oct;9(10):714-23
19730431
Genes Dev. 1998 Sep 15;12(18):2831-41
9744860
Cell. 2004 Jul 9;118(1):83-97
15242646
EMBO Rep. 2009 Jun;10(6):576-83
19424293
Cell Cycle. 2007 Jun 1;6(11):1304-6
17534149
Biochemistry. 2007 Nov 6;46(44):12594-603
17939684
Oncogene. 2009 May 21;28(20):2112-8
19363523
Science. 2003 Dec 12;302(5652):1972-5
14671306
J Exp Med. 2005 Jan 17;201(2):279-89
15642743
Biochemistry. 2009 Mar 17;48(10):2115-24
19220000
EMBO J. 2009 Jul 22;28(14):2100-13
19536131
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6048-53
9177166
Mol Cell Proteomics. 2009 Jun;8(6):1167-73
19155208
Nature. 1995 Nov 9;378(6553):206-8
7477327
J Biol Chem. 2003 Sep 26;278(39):37536-44
12860987
J Neurosci. 2008 Aug 27;28(35):8772-84
18753379
Nat Rev Cancer. 2004 Oct;4(10):793-805
15510160
Nature. 2006 Nov 30;444(7119):629-32
17108971
Mol Cell. 2007 Mar 9;25(5):725-38
17349958
Mol Cell Biol. 2003 Dec;23(23):8846-61
14612423
Nat Cell Biol. 2002 Jan;4(1):11-9
11780126
Oncogene. 1997 Aug 14;15(7):807-16
9266967
Cell. 2009 May 1;137(3):413-31
19410540
Biochem J. 2001 Oct 15;359(Pt 2):459-64
11583595
J Biol Chem. 1999 Sep 10;274(37):26321-8
10473588
Oncogene. 1999 Jan 7;18(1):189-99
9926934
EMBO Rep. 2001 Feb;2(2):139-44
11258706
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6
19556538
Cell. 2008 May 16;133(4):612-26
18485870
Science. 2007 Feb 9;315(5813):840-3
17234915
Cell Cycle. 2007 May 2;6(9):1006-10
17457049
Oncogene. 1999 Dec 13;18(53):7666-75
10618706
Mol Cell. 2006 Sep 1;23(5):757-64
16949371
Biochemistry. 2009 Feb 17;48(6):1244-55
19166313
J Biol Chem. 2007 May 11;282(19):14616-25
17371868
Nature. 1997 Jun 19;387(6635):819-23
9194564
J Biol Chem. 2000 Jul 28;275(30):23199-203
10930428
Structure. 2009 Feb 13;17(2):202-10
19217391
EMBO J. 2000 Dec 1;19(23):6517-26
11101524
Nat Rev Mol Cell Biol. 2008 Mar;9(3):206-18
18292778
Cancer Res. 2005 May 1;65(9):3610-6
15867355
J Biol Chem. 2002 Mar 15;277(11):9054-61
11782467
Nature. 1992 Jul 2;358(6381):15-6
1614522
Oncogene. 1997 Oct 2;15(14):1727-36
9349507
Mol Cell. 2006 Feb 3;21(3):307-15
16455486
J Biol Chem. 1998 Dec 4;273(49):33048-53
9830059
J Mol Biol. 2008 Feb 8;376(1):8-12
18155245
Cancer Cell. 2008 May;13(5):454-63
18455128
EMBO J. 1999 Nov 15;18(22):6462-71
10562558
Nat Cell Biol. 2002 Jan;4(1):1-10
11740489
Mech Ageing Dev. 2007 Apr;128(4):293-302
17291568
Mol Cell Biol. 2005 Jul;25(13):5389-95
15964796
Curr Opin Genet Dev. 2009 Feb;19(1):18-24
19179064
Eur J Biochem. 2001 May;268(10):2764-72
11358490
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6591-6
19357310
EMBO J. 2004 Sep 15;23(18):3689-99
15343266
EMBO J. 2002 Nov 15;21(22):6236-45
12426395
Nature. 1997 Jun 19;387(6635):823-7
9194565
Science. 2003 Apr 11;300(5617):342-4
12690203
Mol Cell Biol. 2007 Oct;27(19):6756-69
17646389
Mol Cell. 2001 Jul;8(1):57-69
11511360
Nat Cell Biol. 2008 Dec;10(12):1431-9
19011621
EMBO J. 2001 Mar 15;20(6):1331-40
11250899
Cell. 1997 Jun 27;89(7):1175-84
9215639
Cell Cycle. 2008 Aug 15;7(16):2519-28
18719371
J Biol Chem. 2009 Jul 24;284(30):20197-205
19494119
J Biol Chem. 2004 Nov 19;279(47):49395-405
15337767
Cell. 1997 Oct 31;91(3):325-34
9363941
Trends Cell Biol. 2002 Sep;12(9):404-6
12220851
Nat Rev Cancer. 2009 Feb;9(2):123-8
19132007
Mol Cell. 2006 Jun 23;22(6):783-794
16793547
Mol Cell. 2006 Dec 28;24(6):841-51
17189187
Cell. 1997 Aug 22;90(4):595-606
9288740
Cancer Res. 2007 Mar 1;67(5):2274-9
17332358
Nucleic Acids Res. 1984 Jul 25;12(14):5609-26
6379601
Nat Genet. 2002 Jun;31(2):133-4
12021784
FEBS Lett. 1999 Dec 17;463(3):312-6
10606744
Mol Cell. 2008 Feb 15;29(3):392-400
18280244
J Biol Chem. 2003 Jul 11;278(28):25568-76
12724314
J Biol Chem. 2002 Dec 27;277(52):50607-11
12421820
J Biol Chem. 2009 Aug 7;284(32):21728-37
19525231
J Cell Sci. 2007 Feb 1;120(Pt 3):371-8
17251377
Cancer Cell. 2006 Dec;10(6):501-14
17157790
Mol Cell Biol. 2007 Feb;27(4):1425-32
17158931
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):106-11
18160537
Mol Cell Biol. 2004 Oct;24(20):8884-94
15456863
Cancer Cell. 2007 Oct;12(4):342-54
17936559
Gene. 2005 Dec 19;363:15-23
16289629
Cell. 2008 May 30;133(5):930-30.e1
18510935
EMBO J. 1999 Apr 1;18(7):1805-14
10202144
Cell. 2009 Apr 3;137(1):87-98
19345189
Cancer Metastasis Rev. 2008 Jun;27(2):123-35
18265945
J Mol Biol. 2002 Oct 25;323(3):491-501
12381304
Mol Cell Biol. 2006 Dec;26(23):8901-13
17000756
Mol Cell. 2007 Aug 17;27(4):636-46
17707234
EMBO J. 2006 Jun 7;25(11):2615-22
16757976
Mol Cell. 1998 Oct;2(4):405-15
9809062
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2872-7
11867732
Mol Cell Biol. 1999 Feb;19(2):1202-9
9891054
Nat Genet. 2002 Jun;31(2):210-5
12021785
Cancer Res. 2003 Aug 1;63(15):4310-4
12907596
Cell. 2009 May 15;137(4):609-22
19450511
EMBO J. 1999 Dec 1;18(23):6845-54
10581258
Oncogene. 1999 Nov 4;18(46):6305-12
10597229
Nat Rev Cancer. 2006 Dec;6(12):909-23
17128209
Mol Cell. 2005 Apr 29;18(3):283-93
15866171
Mol Cell. 2001 Sep;8(3):713-8
11583632
Proc Natl Acad Sci U S A. 1986 Feb;83(4):897-901
3006031