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)

Citation
Jp. Roperch et al., 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), P NAS US, 96(14), 1999, pp. 8070-8073
Citations number
27
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
14
Year of publication
1999
Pages
8070 - 8073
Database
ISI
SICI code
0027-8424(19990706)96:14<8070:SPAATS>2.0.ZU;2-X
Abstract
We have previously described biological model systems for studying tumor su ppression in which, by using H-1 parvovirus as a selective agent, cells wit h a strongly suppressed malignant phenotype (KS or US) were derived from ma lignant cell lines (K562 or U937). By using cDNA display on the K562/KS cel ls, 15 cDNAs were now isolated, corresponding to genes differentially regul ated in tumor suppression. Of these, TSAP9 corresponds to a TCP-1 chaperoni n, TSAP13 to a regulatory proteasome subunit, and TSAP21 to syntaxin 11, a vesicular trafficking molecule. The 15 cDNAs were used as a molecular finge rprint in different tumor-suppression models. We found that a similar patte rn 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 enco ded by SIAH-1, can induce apoptosis and promote tumor suppression. These re sults 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 traf ficking.