p53 and little brother p53/47: linking IRES activities with protein functions

The tumor suppressor p53 represents a paradigm for gene regulation. Its rapid induction in response to DNA damage conditions has been attributed to both increased half-life of p53 protein and also increased translation of p53 mRNA. Recent advances in our understanding of the post-transcriptional regulation of p53 include the discovery of internal ribosome entry sites (IRESs) within the p53 mRNA. These IRES elements regulate the translation of the full length as well as the N-terminally truncated isoform, p53/47. The p53/47 isoform is generated by alternative initiation at an internal AUG codon present within the p53 ORF. The aim of this review is to summarize the role of translational control mechanisms in regulating p53 functions. We discuss here in detail how diverse cellular stress pathways trigger alterations in the cap-dependent and cap-independent translation of p53 mRNA and how changes in the relative expression levels of p53 isoforms result in more differentiated p53 activity.

Higher spin resolution of a toy big bang

Diffeomorphisms preserve spacetime singularities, whereas higher spin symmetries need not. Since three-dimensional de Sitter space has quotients that have big-bang/big-crunch singularities and since dS(3)-gravity can be written as an SL(2, C) Chern-Simons theory, we investigate SL(3, C) Chern-Simons theory as a higher-spin context in which these singularities might get resolved. As in the case of higher spin black holes in AdS(3), the solutions are invariantly characterized by their holonomies. We show that the dS(3) quotient singularity can be desingularized by an SL(3, C) gauge transformation that preserves the holonomy: this is a higher spin resolution the cosmological singularity. Our work deals exclusively with the bulk theory, and is independent of the subtleties involved in defining a CFT2 dual to dS(3) in the sense of dS/CFT.