p53 tetramerization: at the center of the dominant-negative effect of mutant p53

被引:68
作者
Gencel-Augusto, Jovanka [1 ,2 ]
Lozano, Guillermina [1 ,2 ]
机构
[1] Univ TexasMDAnderson Canc Ctr, Genet & Epigenet Grad Program, UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
tetramerization; transcription factor; tumor suppressor; WILD-TYPE P53; TUMOR-SUPPRESSOR PROTEIN; BORDERLINE OVARIAN-TUMORS; BETA-STRAND; 326-333; DNA-BINDING DOMAIN; MISSENSE MUTATION; BREAST-CANCER; LI-FRAUMENI; OLIGOMERIZATION DOMAIN; NUCLEAR EXPORT;
D O I
10.1101/gad.340976.120
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The p53 tumor suppressor functions as a tetrameric transcription factor to regulate hundreds of genes-many in a tissue-specific manner. Missense mutations in cancers in the p53 DNA-binding and tetramerization domains cement the importance of these domains in tumor suppression. p53 mutants with a functional tetramerization domain form mixed tetramers, which in some cases have dominant-negative effects (DNE) that inactivate wild-type p53. DNA damage appears necessary but not sufficient for DNE, indicating that upstream signals impact DNE. Posttranslational modifications and protein-protein interactions alter p53 tetramerization affecting transcription, stability, and localization. These regulatory components limit the dominant-negative effects of mutant p53 on wild-type p53 activity. A deeper understanding of the molecular basis for DNE may drive development of drugs that release WT p53 and allow tumor suppression.
引用
收藏
页码:1128 / 1146
页数:19
相关论文
共 135 条
[51]   THERMODYNAMIC ANALYSIS OF THE STRUCTURAL STABILITY OF THE TETRAMERIC OLIGOMERIZATION DOMAIN OF P53 TUMOR-SUPPRESSOR [J].
JOHNSON, CR ;
MORIN, PE ;
ARROWSMITH, CH ;
FREIRE, E .
BIOCHEMISTRY, 1995, 34 (16) :5309-5316
[52]   Tetramer Formation of Tumor Suppressor Protein p53: Structure, Function, and Applications [J].
Kamada, Rui ;
Toguchi, Yu ;
Nomura, Takao ;
Imagawa, Toshiaki ;
Sakaguchi, Kazuyasu .
BIOPOLYMERS, 2016, 106 (04) :598-612
[53]   Cancer-associated p53 Tetramerization Domain Mutants QUANTITATIVE ANALYSIS REVEALS A LOW THRESHOLD FOR TUMOR SUPPRESSOR INACTIVATION [J].
Kamada, Rui ;
Nomura, Takao ;
Anderson, Carl W. ;
Sakaguchi, Kazuyasu .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (01) :252-258
[54]   Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation [J].
Kanai, Masayuki ;
Hanashiro, Kazuhiko ;
Kim, Song-Hee ;
Hanai, Shuji ;
Boulares, A. Hamid ;
Miwa, Masanao ;
Fukasawa, Kenji .
NATURE CELL BIOLOGY, 2007, 9 (10) :1175-1183
[55]   Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation [J].
Kapoor, M ;
Lozano, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) :2834-2837
[56]   Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis [J].
Kato, S ;
Han, SY ;
Liu, W ;
Otsuka, K ;
Shibata, H ;
Kanamaru, R ;
Ishioka, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (14) :8424-8429
[57]   Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers [J].
Katz, Chen ;
Low-Calle, Ana Maria ;
Choe, Joshua H. ;
Laptenko, Oleg ;
Tong, David ;
Joseph-Chowdhury, Jazmine-Saskya N. ;
Garofalo, Francesca ;
Zhu, Yan ;
Friedler, Assaf ;
Prives, Carol .
GENES & DEVELOPMENT, 2018, 32 (5-6) :430-447
[58]   The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library [J].
Kawaguchi, T ;
Kato, S ;
Otsuka, K ;
Watanabe, G ;
Kumabe, T ;
Tominaga, T ;
Yoshimoto, T ;
Ishioka, C .
ONCOGENE, 2005, 24 (46) :6976-6981
[59]   ONCOGENIC FORMS OF P53 INHIBIT P53-REGULATED GENE-EXPRESSION [J].
KERN, SE ;
PIETENPOL, JA ;
THIAGALINGAM, S ;
SEYMOUR, A ;
KINZLER, KW ;
VOGELSTEIN, B .
SCIENCE, 1992, 256 (5058) :827-830
[60]   Reduced latency but no increased brain tumor penetrance in mice with astrocyte specific expression of a human p53 mutant [J].
Klein, MA ;
Rüedi, D ;
Nozaki, M ;
Dell, EW ;
Diserens, AC ;
Seelentag, W ;
Janzer, RC ;
Aguzzi, A ;
Hegi, ME .
ONCOGENE, 2000, 19 (47) :5329-5337