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

• Published in: Oncogene Vol. 23; no. 56; pp. 9007 - 9016
• Main Authors: SLEE, Elizabeth A, GILLOTIN, Sébastien, BERGAMASCHI, Daniele, ROYER, Christophe, LLANOS, Susana, ALI, Safia, BOQUAN JIN, TRIGIANTE, Giuseppe, XIN LU
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 02-12-2004; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing; Ageing, cell death; Amino Acid Sequence; Amino acids; Apoptosis; Apoptosis - physiology; Apoptosis Regulatory Proteins; Base Sequence; Biological and medical sciences; Cancer research; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell cycle; Cell death; Cell division; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cytoplasm; Cytoplasm - metabolism; DNA damage; DNA Primers; Fundamental and applied biological sciences. Psychology; Humans; Localization; Medical research; Molecular and cellular biology; Molecular Sequence Data; N-Terminus; Nematodes; p53 Protein; Protein Isoforms - chemistry; Protein Isoforms - metabolism; Proteins; Sequence Homology, Amino Acid; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Protein p53 - physiology; Human; Molecular form; TP53 Gene; Localization; Carcinogenesis; iASPP; Apoptosis; Tumor suppressor gene; p53
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208088

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.