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Molecular and Cellular Biology, February 2004, p. 1341-1350, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1341-1350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ASPP1 and ASPP2: Common Activators of p53 Family Members

Daniele Bergamaschi,1,{dagger} Yardena Samuels,1,{dagger} Boquan Jin,2 Sai Duraisingham,1 Tim Crook,1 and Xin Lu1*

Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom,1 Department of Immunology, Fourth Military Medical University, Xian 710032, People's Republic of China2

Received 6 June 2003/ Returned for modification 31 July 2003/ Accepted 6 November 2003

We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21WAF-1/CIP1. The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21WAF-1/CIP1. Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.

* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 442075637710. Fax: 442077248586. E-mail: x.lu{at}ic.ac.uk.

{dagger} D.B. and Y.S. contributed equally to this study.

Molecular and Cellular Biology, February 2004, p. 1341-1350, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1341-1350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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