The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization

Abstract

ASPP1 and ASPP2 are both proteins that interact with p53 and enhance its ability to induce apoptosis by selectively elevating the expression of proapoptotic p53-responsive genes. iASPP(RAI) is a third member of the family that is the most conserved inhibitor of p53-mediated apoptosis. Here, we have described iASPP, a longer form of iASPP(RAI), which at 828 amino acids is more than twice the size of iASPP(RAI). Using two antibodies that recognize both iASPP and iASPP(RAI), we report that this longer form of iASPP is the predominant form of the molecule expressed in cells. Like iASPP(RAI), iASPP also binds to p53 and inhibits apoptosis induced by p53 overexpression. However, whereas iASPP(RAI) is predominantly nuclear, the N-terminus of iASPP is entirely cytoplasmic, and the longer iASPP is located in both the cytoplasm and the nucleus. The effect upon subcellular localization of the longer N-terminus of iASPP means that this new, longer form of the molecule may be subject to greater regulation and provides another layer in the control of p53-induced apoptosis.

The tumour-suppressor protein ASPP1 is nuclear in human germ cells and can modulate ratios of CD44 exon V5 spliced isoforms in vivo

“…GFP protein fusions containing the hASPP1 N-terminus (1-356 and 1-531) had a general distribution throughout the cell (compare DAPI staining pattern with ASPP1-GFP). Similar results have been reported for other members of the ASPP family (Yang et al, 1999;Bergamaschi et al, 2003;Slee et al, 2004).…”

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

“…Originally, iASPP was identified as a Rel A/ p65 associated inhibitor (RAI) of 315 amino acids in length (Yang et al, 1999). Subsequent studies demonstrated full length of RAI protein, iASPP containing 828 amino acids in humans and in C. elegans its homologoue is named as Ce-iASPP containing 769 amino acids encoded by ape-1 gene (Bergamaschi et al, 2003;Slee et al, 2004).…”

Some p53-binding proteins that can function as arbiters of life and death

“…25 While the N-terminals of ASPP1 and ASPP2 are very similar, they share no sequence similarity with that of iASPP. 27 The precise details underlying the mechanism of the proapoptotic function of the N-terminus of ASPP1 and ASPP2 are currently unknown. Nevertheless, when intact ASPP1 or ASPP2 binds p53, they can specifically enhance the ability of p53 to induce apoptosis but not cell cycle arrest.…”