Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Selected targets of p53


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Selected targets of p53

Selected targets of p53

Tumor protein p53 ( p53 ) is active as a tetramer consisting of four identicalchains of 393 amino acid residues. The N-terminal region contains an intrinsicallydisordered trans-activation domain (TAD) and a proline-rich region. The central, foldedDNA-binding core domain, is responsible for sequence-specific DNA binding. At itsC-terminus, p53 contains the so-called regulatory domain. This natively unfoldedregion is rich in basic amino acids (mainly lysines) and binds DNA nonspecifically [1].

p53 is normally activated by cellular stress and mediates thegrowth-suppressive response that involves cell cycle arrest and apoptosis [2]. In the case of cell cycle arrest, Cyclin-dependent kinase inhibitor 1A (p21 ) appears sufficient to block cell cycle progression out of G1 until DNArepair has occurred, or the cellular stress has been alleviated [3], [2].

The p53 -dependent apoptotic response is complex and involves transcriptionalactivation of multiple pro-apoptotic target genes [2]. There are, forexample, different caspases [4], Cathepsin D [5], Bcl-2family members (B-cell CLL/lymphoma 2 ( Bcl-2 ) and BCL2-associated X protein (Bax )) [6] and BCL2/adenovirus E1B 19kDa interacting protein 3-like (NIX ) [7].

The p53 pathway, either directly or indirectly, is targeted for inactivationin most human cancers. The latter highlights the protein's critical function as a tumorsuppressor gene [2]. This pathway is realized mostly via regulation oftranscription of developmental signaling genes. for example of tumor suppressorsHypermethylated in cancer 1 and 2 ( HIC1/2 ) [8], Brain-specificangiogenesis inhibitor 1 ( BAI1 ) [9], PTK6 protein tyrosine kinase 6( BRK ) [10], Adenomatous polyposis coli ( APC protein ) [11].

In addition, p53 participates in regulation of transport [12],cytoskeletal signaling [13], ECM and adhesion [14], proteintraffic [15] and others processes. Possibly, most of these processes takepart in development of the basic p53 -denendent response (apoptosis, cell cyclearrest, tumor suppression).