DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo

被引:47
作者
Jabbur, JR
Huang, P
Zhang, W
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Clin Invest, Houston, TX 77030 USA
关键词
phosphorylation; ionizing radiation; p53; p21;
D O I
10.1038/sj.onc.1204017
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
We investigated the induction and physiological role of Ser20 phosphorylation of p53 in response to DNA damage caused by ionizing radiation (IR) or ultraviolet radiation (UV), A polyclonal antibody that specifically recognizes a p53 peptide containing phosphorylated Ser20 was generated and used to detect p53 phosphorylation at Ser20, Western blot analyses of p53 in four cell lines with this antibody revealed that the p53 protein was phosphorylated at Ser20 to a different extent after treatment with IR or UV, The phosphorylation of Ser20 of wild-type p53 correlated with enhanced induction of the p53 downstream target genes p21(WAF1/Cip1) (p21) and mdm-2. These results suggest that DNA damage-induced phosphorylation of p53 at Ser20 enhances the transactivation function of p53 for p21 and mdm-2 in vivo.
引用
收藏
页码:6203 / 6208
页数:6
相关论文
共 48 条
[1]  
Ashcroft M, 1999, MOL CELL BIOL, V19, P1751
[2]   Enhanced phosphorylation of p53 by ATN in response to DNA damage [J].
Banin, S ;
Moyal, L ;
Shieh, SY ;
Taya, Y ;
Anderson, CW ;
Chessa, L ;
Smorodinsky, NI ;
Prives, C ;
Reiss, Y ;
Shiloh, Y ;
Ziv, Y .
SCIENCE, 1998, 281 (5383) :1674-1677
[3]   Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation [J].
Bulavin, DV ;
Saito, S ;
Hollander, MC ;
Sakaguchi, K ;
Anderson, CW ;
Appella, E ;
Fornace, AJ .
EMBO JOURNAL, 1999, 18 (23) :6845-6854
[4]   Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J].
Canman, CE ;
Lim, DS ;
Cimprich, KA ;
Taya, Y ;
Tamai, K ;
Sakaguchi, K ;
Appella, E ;
Kastan, MB ;
Siliciano, JD .
SCIENCE, 1998, 281 (5383) :1677-1679
[5]  
Chehab NH, 2000, GENE DEV, V14, P278
[6]   Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage [J].
Chehab, NH ;
Malikzay, A ;
Stavridi, ES ;
Halazonetis, TD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :13777-13782
[7]  
Chen JD, 1996, MOL CELL BIOL, V16, P2445
[8]   Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15 [J].
Dumaz, N ;
Milne, DM ;
Meek, DW .
FEBS LETTERS, 1999, 463 (03) :312-316
[9]   Regulation of p53 downstream genes [J].
El-Deiry, WS .
SEMINARS IN CANCER BIOLOGY, 1998, 8 (05) :345-357
[10]   The complexity of p53 modulation: emerging patterns from divergent signals [J].
Giaccia, AJ ;
Kastan, MB .
GENES & DEVELOPMENT, 1998, 12 (19) :2973-2983