Mutant p53 proteins bind DNA in a DNA structure-selective mode.
Despite the loss of sequence-specific DNA binding, mutant p53 (mutp53) proteins can induce or repress transcription of mutp53-specific target genes. To date, the molecular basis for transcriptional modulation by mutp53 is not understood, but increasing evidence points to the possibility that specific interactions of mutp53 with DNA play an important role. So far, the lack of a common denominator for mutp53 DNA binding, i.e. the existence of common sequence elements, has hampered further characterization of mutp53 DNA binding. Emanating from our previous discovery that DNA structure is an important determinant of wild-type p53 (wtp53) DNA binding, we analyzed the binding of various mutp53 proteins to oligonucleotides mimicking non-B DNA structures. Using various DNA-binding assays we show that mutp53 proteins bind selectively and with high affinity to non-B DNA. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, mutp53 DNA binding to non-B DNA is solely dependent on the stereo-specific configuration of the DNA, and not on DNA sequence. We propose that DNA structure-selective binding of mutp53 proteins is the basis for the well-documented interaction of mutp53 with MAR elements and for transcriptional activities mediates by mutp53.
Göhler
Thomas
T
Department of Tumor Virology, Heinrich-Pette-Institute Martinistrasse 52, 20251 Hamburg, Germany.
Jäger
Stefan
S
Warnecke
Gabriele
G
Yasuda
Hideyo
H
Kim
Ella
E
Deppert
Wolfgang
W
D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D009154:Mutation; D009690:Nucleic Acid Conformation; D040081:Protein Array Analysis; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004247:DNA
Crit Rev Eukaryot Gene Expr. 2000;10(1):45-61
10813394
J Mol Biol. 2000 Jun 9;299(3):585-92
10835269
Oncogene. 2000 Aug 3;19(33):3717-26
10949925
Oncogene. 2000 Aug 24;19(36):4178-83
10962580
Biochem Biophys Res Commun. 2000 Dec 20;279(2):383-90
11118296
Cell. 1995 Jun 30;81(7):1013-20
7600570
J Biol Chem. 1995 Aug 25;270(34):19680-3
7649977
Oncogene. 1996 May 2;12(9):1941-52
8649855
J Biol Chem. 1997 Mar 14;272(11):7532-9
9054458
J Biol Chem. 1997 Jun 6;272(23):14842-9
9169453
Oncogene. 1997 Aug 14;15(7):857-69
9266973
Mol Cell Biol. 1997 Nov;17(11):6255-64
9343386
Cell Mol Biol (Noisy-le-grand). 1997 Nov;43(7):935-49
9449526
Oncogene. 1998 Feb 5;16(5):685-90
9482117
Mol Cell Biol. 1998 Jul;18(7):3735-43
9632756
Oncogene. 1998 Jun 18;16(24):3169-76
9671396
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13681-6
9811860
EMBO J. 1999 Jan 4;18(1):22-7
9878046
Differentiation. 1999 May;64(4):205-12
10365438
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10355-60
10468612
Mol Cell. 2004 Nov 5;16(3):413-24
15525514
Cancer Res. 2000 Dec 15;60(24):6788-93
11156366
J Biol Chem. 2001 Mar 23;276(12):8778-84
11124254
J Biol Chem. 2001 May 11;276(19):15650-8
11279079
J Cell Biochem Suppl. 2000;Suppl 35:115-22
11389540
Mol Cell. 2001 Jul;8(1):57-69
11511360
Oncogene. 2001 Aug 9;20(35):4891-8
11521201
Oncogene. 2001 Sep 6;20(39):5449-58
11571642
J Biol Chem. 2001 Oct 19;276(42):39359-67
11483599
J Biomol Screen. 2001 Oct;6(5):275-90
11689128
J Biol Chem. 2002 Apr 5;277(14):11625-8
11859067
Cancer Res. 2002 Jun 1;62(11):3264-70
12036943
Nat Rev Cancer. 2002 Aug;2(8):594-604
12154352
Mol Cell Biol. 2002 Oct;22(19):6797-808
12215537
J Biol Chem. 2002 Oct 25;277(43):41192-203
12171916
Trends Biochem Sci. 2002 Dec;27(12):612-8
12468230
Cancer Cell. 2003 Feb;3(2):145-60
12620409
Cancer Res. 2003 May 15;63(10):2616-23
12750288
J Biol Chem. 2003 Jun 27;278(26):24108-12
12700230
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9
12826609
Drug Discov Today. 2003 Jul 15;8(14):632-41
12867149
Biochem Cell Biol. 2003 Jun;81(3):141-50
12897847
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9934-9
12909720
J Biol Chem. 2003 Aug 29;278(35):32587-95
12813031
Oncogene. 2003 Aug 28;22(36):5667-76
12944915
Oncogene. 2003 Oct 30;22(49):7716-27
14586398
Cancer Sci. 2004 Jan;95(1):7-11
14720320
Oncogene. 2004 May 27;23(25):4430-43
15077194
J Biol Chem. 2004 Jul 9;279(28):29841-8
15090541
Oncogene. 1999 Dec 2;18(51):7310-8
10602486
Mol Cell Biol. 2000 Mar;20(6):2023-30
10688649
Cell. 1988 Oct 7;55(1):79-89
3167979
Oncogene. 1992 Oct;7(10):1921-32
1408133
Genes Dev. 1993 Dec;7(12B):2575-86
8276240
Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):413-7
8278402
Science. 1995 Jan 6;267(5194):100-4
7809597
Nucleic Acids Res. 1995 Feb 11;23(3):362-9
7885831
Mol Cell Biol. 1995 Jun;15(6):3450-9
7760842
Proc Natl Acad Sci U S A. 1995 May 23;92(11):5154-8
7761466
Oncogene. 1995 Jun 15;10(12):2387-90
7784087