Biomaterial Database

The WTX tumor suppressor enhances p53 acetylation by CBP/p300. 2012

Woo Jae Kim, and Miguel N Rivera, and Erik J Coffman, and Daniel A Haber

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in β-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53, and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA-binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 373/382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell-cycle arrest, apoptosis, and p53 target-gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000107	Acetylation	Formation of an acetyl derivative. (Stedman, 25th ed)	Acetylations
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D048868	Adaptor Proteins, Signal Transducing	A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes	Signal Transducing Adaptor Proteins
D050880	p300-CBP Transcription Factors	A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.	p300-CBP Coactivator,p300-CBP Protein,Coactivator, p300-CBP,Transcription Factors, p300-CBP,p300 CBP Coactivator,p300 CBP Protein,p300 CBP Transcription Factors
D055550	Protein Stability	The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.	Protein Stabilities,Stabilities, Protein,Stability, Protein
D057809	HEK293 Cells	A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.	293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D025521	Tumor Suppressor Proteins	Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.	Growth Suppressor Proteins,Metastasis Suppressor Protein,Metastasis Suppressor Proteins,Tumor Suppressor Protein,Protein, Metastasis Suppressor,Protein, Tumor Suppressor,Proteins, Growth Suppressor,Proteins, Metastasis Suppressor,Proteins, Tumor Suppressor,Suppressor Protein, Metastasis,Suppressor Protein, Tumor