Biomaterial Database

A novel transcriptional repression domain mediates p21(WAF1/CIP1) induction of p300 transactivation. 2000

A W Snowden, and L A Anderson, and G A Webster, and N D Perkins

Division of Gene Regulation and Expression, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.

The transcriptional coactivators p300 and CREB binding protein (CBP) are important regulators of the cell cycle, differentiation, and tumorigenesis. Both p300 and CBP are targeted by viral oncoproteins, are mutated in certain forms of cancer, are phosphorylated in a cell cycle-dependent manner, interact with transcription factors such as p53 and E2F, and can be found complexed with cyclinE-Cdk2 in vivo. Moreover, p300-deficient cells show defects in proliferation. Here we demonstrate that transcriptional activation by both p300 and CBP is stimulated by coexpression of the cyclin-dependent kinase inhibitor p21(WAF/CIP1). Significantly this stimulation is independent of both the inherent histone acetyltransferase (HAT) activity of p300 and CBP and of the previously reported carboxyl-terminal binding site for cyclinE-Cdk2. Rather, we describe a previously uncharacterized transcriptional repression domain (CRD1) within p300. p300 transactivation is stimulated through derepression of CRD1 by p21. Significantly p21 regulation of CRD1 is dependent on the nature of the core promoter. We suggest that CRD1 provides a novel mechanism through which p300 and CBP can switch activities between the promoters of genes that stimulate growth and those that enhance cell cycle arrest.

UI	MeSH Term	Description	Entries
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002453	Cell Cycle	The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.	Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015533	Transcriptional Activation	Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.	Gene Activation,Genetic Induction,Transactivation,Induction, Genetic,Trans-Activation, Genetic,Transcription Activation,Activation, Gene,Activation, Transcription,Activation, Transcriptional,Genetic Trans-Activation,Trans Activation, Genetic
D015534	Trans-Activators	Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.	Nuclear Trans-Acting Factor,Trans-Acting Factors,Trans-Acting Factor,Trans-Activator,Transactivator,Transactivators,Factor, Nuclear Trans-Acting,Factor, Trans-Acting,Factors, Trans-Acting,Nuclear Trans Acting Factor,Trans Acting Factor,Trans Acting Factors,Trans Activator,Trans Activators,Trans-Acting Factor, Nuclear
D016213	Cyclins	A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.	Cyclin
D050759	Cyclin-Dependent Kinase Inhibitor p21	A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.	CDK2-Associated Protein 20 kDa,CDKN1 Protein,CDKN1A Protein,Cdk-Interacting Protein 1,Cdk2 Inhibitor Protein,Cell Cycle Regulator p21,Cyclin Kinase Inhibitor p21,Cyclin-Dependent Kinase Inhibitor 1A Protein,Senescent Cell-Derived Inhibitor Protein 1,p21 Cell Cycle Regulator,p21 Cyclin Kinase Inhibitor,CDK2 Associated Protein 20 kDa,Cdk Interacting Protein 1,Cyclin Dependent Kinase Inhibitor 1A Protein,Cyclin Dependent Kinase Inhibitor p21,Senescent Cell Derived Inhibitor Protein 1
D050882	CREB-Binding Protein	A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.	Nuclear Protein CBP,Phospho-CREB-Binding Protein,CBP, Nuclear Protein,CREB Binding Protein,Phospho CREB Binding Protein