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Polypyrimidine tract binding protein regulates IRES-mediated translation of p53 isoforms

Grover, Richa and Ray, Partho Sarothi and Das, Saumitra (2008) Polypyrimidine tract binding protein regulates IRES-mediated translation of p53 isoforms. In: Cell Cycle, 7 (14). pp. 2189-2198.

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Abstract

The p53 tumor suppressor protein plays a key role in maintaining genomic integrity. Enhanced expression of p53 during genotoxic stress is due to both increased protein stability and translational up regulation. Previous reports have shown that p53 mRNA is translated from an alternative initiation codon to produce N-terminal truncated isoform $(\Delta N-p53)$ besides full-length p53. We have demonstrated that two internal ribosome entry sites (IRESs) regulate the translation of p53 and $\Delta N-p53$ in a distinct cell-cycle phase-dependent manner. Here, we report that polypyrimidine tract-binding protein (PTB) is a p53 IRES interacting trans-acting factor. PTB protein binds specifically to both the p53 IRESs but with differential affinity. siRNA-mediated knockdown of PTB protein results in reduction of activity of both IRESs and also the levels of both the isoforms. It is well known that DNA-damaging agents such as doxorubicin enhance the expression of p53. Our results indicate that during doxorubicin treatment, PTB protein translocates from nucleus to the cytoplasm, probably to facilitate IRES mediated p53 translation. These observations suggest that the relative cytoplasmic abundance of PTB protein, under DNA-damaging conditions, might contribute to regulating the coordinated expression of the p53 isoforms, owing to the differential affinity of PTB binding to the two p53 IRESs.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Landes Bioscience.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 14 Oct 2008 04:52
Last Modified: 14 Oct 2008 04:52
URI: http://eprints.iisc.ernet.in/id/eprint/15988

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