Priority Research Papers:

Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-κB

Ying Hu, Wenjie Ge, Xingwen Wang, Gopinath Sutendra, Kunming Zhao, Zinaida Dedeić, Elizabeth A. Slee, Caroline Baer and Xin Lu _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:42478-42490. https://doi.org/10.18632/oncotarget.6478

Metrics: PDF 1760 views  |   HTML 2180 views  |   ?  


Ying Hu1,2, Wenjie Ge1, Xingwen Wang1, Gopinath Sutendra2, Kunming Zhao1, Zinaida Dedeić2, Elizabeth A. Slee2, Caroline Baer2 and Xin Lu2

1 The School of Life Science and Technology, Harbin Institute of Technology, Harbin, China

2 Ludwig Institute for Cancer Research Ltd., Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

Correspondence to:

Xin Lu, email:

Ying Hu, email:

Keywords: iASPP, caspase, p53, RelA/p65

Received: July 09, 2015 Accepted: November 25, 2015 Published: December 05, 2015


An intriguing biological question relating to cell signaling is how the inflammatory mediator NF-kB and the tumour suppressor protein p53 can be induced by similar triggers, like DNA damage or infection, yet have seemingly opposing or sometimes cooperative biological functions. For example, the NF-κB subunit RelA/p65 has been shown to inhibit apoptosis, whereas p53 induces apoptosis. One potential explanation may be their co-regulation by common cellular factors: inhibitor of Apoptosis Stimulating p53 Protein (iASPP) is one such common regulator of both RelA/p65 and p53. Here we show that iASPP is a novel substrate of caspases in response to apoptotic stimuli. Caspase cleaves the N-terminal region of iASPP at SSLD294 resulting in a prominent 80kDa fragment of iASPP. This caspase cleavage site is conserved in various species from zebrafish to Homo sapiens. The 80kDa fragment of iASPP translocates from the cytoplasm to the nucleus via the RaDAR nuclear import pathway, independent of p53. The 80kDa iASPP fragment can bind and inhibit p53 or RelA/p65 more efficiently than full-length iASPP. Overall, these data reveal a potential novel regulation of p53 and RelA/p65 activities in response to apoptotic stimuli.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6478