DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization

被引:267
作者
Shieh, SY
Taya, Y
Prives, C [1 ]
机构
[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
[2] Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 104, Japan
关键词
DNA damage; oligomerization; p53; phosphorylation;
D O I
10.1093/emboj/18.7.1815
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Upon DNA damage, p53 has been shown to be modified at a number of N-terminal phosphorylation sites including Ser15 and -33, Here we show that phosphorylation is induced as well at a novel site, Ser20, Phosphorylation at Ser15, -20 and -33 can occur within minutes of DNA damage. Interestingly, while the DNA-binding activities of p53 appear to be dispensable, efficient phosphorylation at these three sites requires the tetramerization domain of p53, Substitution of an artificial tetramerization domain for this region also permits phosphorylation at the N-terminus, suggesting that oligomerization is important for DNA damage-induced signalling to p53.
引用
收藏
页码:1815 / 1823
页数:9
相关论文
共 71 条
  • [1] The p53 network
    Agarwal, ML
    Taylor, WR
    Chernov, MV
    Chernova, OB
    Stark, GR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (01) : 1 - 4
  • [2] P53 BINDS SINGLE-STRANDED-DNA ENDS THROUGH THE C-TERMINAL DOMAIN AND INTERNAL DNA SEGMENTS VIA THE MIDDLE DOMAIN
    BAKALKIN, G
    SELIVANOVA, G
    YAKOVLEVA, T
    KISELEVA, E
    KASHUBA, E
    MAGNUSSON, KP
    SZEKELY, L
    KLEIN, G
    TERENIUS, L
    WIMAN, KG
    [J]. NUCLEIC ACIDS RESEARCH, 1995, 23 (03) : 362 - 369
  • [3] Enhanced phosphorylation of p53 by ATN in response to DNA damage
    Banin, S
    Moyal, L
    Shieh, SY
    Taya, Y
    Anderson, CW
    Chessa, L
    Smorodinsky, NI
    Prives, C
    Reiss, Y
    Shiloh, Y
    Ziv, Y
    [J]. SCIENCE, 1998, 281 (5383) : 1674 - 1677
  • [4] A PROTEOLYTIC FRAGMENT FROM THE CENTRAL REGION OF P53 HAS MARKED SEQUENCE-SPECIFIC DNA-BINDING ACTIVITY WHEN GENERATED FROM WILD-TYPE BUT NOT FROM ONCOGENIC MUTANT P53-PROTEIN
    BARGONETTI, J
    MANFREDI, JJ
    CHEN, XB
    MARSHAK, DR
    PRIVES, C
    [J]. GENES & DEVELOPMENT, 1993, 7 (12B) : 2565 - 2574
  • [5] CHARACTERIZATION OF THE TUMOR SUPPRESSOR PROTEIN-P53 AS A PROTEIN-KINASE-C SUBSTRATE AND A S100B-BINDING PROTEIN
    BAUDIER, J
    DELPHIN, C
    GRUNWALD, D
    KHOCHBIN, S
    LAWRENCE, JJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (23) : 11627 - 11631
  • [6] DNA damage triggers DRB-resistant phosphorylation of human p53 at the CK2 site
    Blaydes, JP
    Hupp, TR
    [J]. ONCOGENE, 1998, 17 (08) : 1045 - 1052
  • [7] Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
    Canman, CE
    Lim, DS
    Cimprich, KA
    Taya, Y
    Tamai, K
    Sakaguchi, K
    Appella, E
    Kastan, MB
    Siliciano, JD
    [J]. SCIENCE, 1998, 281 (5383) : 1677 - 1679
  • [8] FREQUENT MUTATIONS IN THE P53 TUMOR SUPPRESSOR GENE IN HUMAN LEUKEMIA T-CELL LINES
    CHENG, J
    HAAS, M
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (10) : 5502 - 5509
  • [9] REFINED SOLUTION STRUCTURE OF THE OLIGOMERIZATION DOMAIN OF THE TUMOR-SUPPRESSOR P53
    CLORE, GM
    ERNST, J
    CLUBB, R
    OMICHINSKI, JG
    KENNEDY, WMP
    SAKAGUCHI, K
    APPELLA, E
    GRONENBORN, AM
    [J]. NATURE STRUCTURAL BIOLOGY, 1995, 2 (04): : 321 - 333
  • [10] IKAP is a scaffold protein of the IκB kinase complex
    Cohen, L
    Henzel, WJ
    Baeuerle, PA
    [J]. NATURE, 1998, 395 (6699) : 292 - 296