SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: Identification of common effectors with p53 and p21 Waf1

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-07, Vol.96 (14), p.8070-8073
• Main Authors: Roperch, Jean-Pierre, Lethrone, Florence, Prieur, Sylvie, Piouffre, Laurence, Israeli, David, Tuynder, Marcel, Nemani, Mona, Pasturaud, Patricia, Gendron, Marie-Claude, Dausset, Jean, Oren, Moshe, Amson, Robert B., Telerman, Adam
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.14.8070

We have previously described biological model systems for studying tumor suppression in which, by using H-1 parvovirus as a selective agent, cells with a strongly suppressed malignant phenotype (KS or US) were derived from malignant cell lines (K562 or U937). By using cDNA display on the K562/KS cells, 15 cDNAs were now isolated, corresponding to genes differentially regulated in tumor suppression. Of these, TSAP9 corresponds to a TCP-1 chaperonin, TSAP13 to a regulatory proteasome subunit, and TSAP21 to syntaxin 11, a vesicular trafficking molecule. The 15 cDNAs were used as a molecular fingerprint in different tumor-suppression models. We found that a similar pattern of differential regulation is shared by activation of p53, p21 Waf1 , and the human homologue of Drosophila seven in absentia, SIAH-1. Because SIAH-1 is differentially expressed in the various models, we characterized it at the protein and functional levels. The 32-kDa, mainly nuclear protein encoded by SIAH-1, can induce apoptosis and promote tumor suppression. These results suggest the existence of a common mechanism of tumor suppression and apoptosis shared by p53, p21 Waf1 , and SIAH-1 and involving regulation of the cellular machinery responsible for protein folding, unfolding, and trafficking.