Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that p53 alterations are commonly found in tumour cells. Another marker of tumorigenesis is FAK (focal adhesion kinase), a non-receptor kinase that is overexpressed in many types of tumours. Previously we determined that the N-terminal domain of FAK physically interacted with the N-terminal domain of p53. In the present study, using phage display, sitedirected mutagenesis, pulldown and immunoprecipitation assays we localized the site of FAK binding to a 7-amino-acid region(amino acids 65-71) in the N-terminal proline-rich domain of human p53. Mutation of the binding site in p53 reversed the suppressive effect of FAK on p53-mediated transactivation ofp21, BAX (Bcl-2-associated X protein) and Mdm2 (murine double minute 2) promoters. In addition, to functionally test this p53 site, we conjugated p53 peptides [wild-type (containing the wild-type binding site) and mutant (with a mutated 7-aminoacid binding site)] to a TAT peptide sequence to penetrate the cells, and demonstrated that the wild-type p53 peptide disrupted binding of FAK and p53 proteins and significantly inhibited cell viability of HCT116 p53+/+ cells compared with the control mutant peptide and HCT116 p53-/- cells. Furthermore, the TAT-p53 peptide decreased the viability of MCF-7 cells, whereas the mutant peptide did not cause this effect. Normal fibroblast p53+/+ and p53-/- MEF (murine embryonic fibroblast) cells and breast MCF10A cells were not sensitive to p53 peptide. Thus, for the first time, we have identified the binding site of the p53 andFAK interaction and have demonstrated that mutating this site and targeting the site with peptides affects p53 functioning and viability in the cells.
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PMID:The 7-amino-acid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning. 1821 42

Odontoblasts are involved in tooth repair and regeneration as well as dentin formation. The aim of this study was to examine whether delivery of heat shock protein 27 (Hsp27) into cells using a TAT fusion protein system (TAT-Hsp27) enhances adhesion and migration of murine dental papilla-derived MDPC-23 cells. Hsp27 was delivered into cells by the TAT-fusion protein system. To examine whether TAT-Hsp27 affects the viability of MDPC-23 cells, MTT assay was performed. The effect of TAT-Hsp27 on adhesion and migration of MDPC-23 cells was determined using type I collagen-coated plates and a commercial kit, respectively. In addition, a precise molecular mechanism was examined by Western blot analysis and focal adhesion activity. TAT-fusion protein system delivered Hsp27 into cells successfully. Transduction of TAT-Hsp27 induced adhesion and migration of MDPC-23 cells in a dose-dependent manner. Moreover, transduction of TAT-Hsp27 increased the protein expression of beta1 integrin and focal adhesion formation, and induced phosphorylation of FAK and ERK. TAT-Hsp27-induced migration of MDPC-23 cells was restored by treatment of anti-beta1 integrin antibody. These findings suggest that TAT-Hsp27 promotes adhesion and migration of MDPC-23 cells via beta1 integrin-mediated signaling and is a promising candidate for therapeutic application of dental pulp regeneration.
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PMID:TAT-Hsp27 promotes adhesion and migration of murine dental papilla-derived MDPC-23 cells through beta1 integrin-mediated signaling. 2066 53