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)
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
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.