Anuj Sharma - p53 Amino-terminus region (1-125) stabilizes and restores heat denatured p53 wild phenotype.

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      BACKGROUND: The intrinsically disordered N-ter domain (NTD) of   p53 encompasses approximately hundred amino acids that contain a   transactivation domain (1-73) and a proline-rich domain (64-92)   and is responsible for transactivation function and apoptosis. It   also possesses an auto-inhibitory function as its removal results   in remarkable reduction in dissociation of p53 from DNA.   PRINCIPAL FINDINGS/METHODOLOGY: In this report, we have   discovered that p53-NTD spanning amino acid residues 1-125   (NTD125) interacted with WT p53 and stabilized its wild type   conformation under physiological and elevated temperatures, both   in vitro and in cellular systems. NTD125 prevented irreversible   thermal aggregation of heat denatured p53, enhanced p21-5'-DBS   binding and further restored DBS binding activity of   heat-denatured p53, in vitro, in a dose-dependent manner. In vivo   ELISA and immunoprecipitation analysis of NTD125-transfected   cells revealed that NTD125 shifted equilibrium from p53 mutant to   wild type under heat stress conditions. Further, NTD125 initiated   nuclear translocation of cytoplasmic p53 in transcriptionally   active state in order to activate p53 downstream genes such as   p21, Bax, PUMA, Noxa and SUMO. CONCLUSION/SIGNIFICANCE: Here, we   showed that a novel chaperone-like activity resides in p53-N-ter   region. This study might have significance in understanding the   role of p53-NTD in p53 stabilization, conformational activation   and apoptosis under heat-stress conditions.

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