Abstract
SIAH-1 and SIAH-2 are the human members of an evolutionary highly conserved E3 ligase family. SIAH-1 is a p53 and p21Waf−1/Cip−1 induced gene during apoptosis and tumor suppression. In stable-transfected clones of MCF-7 cells, SIAH-1 overexpression was associated with apoptosis, mitotic alterations and p21Waf−1/Cip−1 induction of expression. Using a two-hybrid screening, we identified here the transcriptional corepressor CtBP-interacting protein (CtIP) as a SIAH-1-interacting protein. CtIP has been proposed as a regulator of p21Waf−1/Cip−1 gene transcription through a protein complex involving BRCA1. We demonstrate that SIAH-1 associates with CtIP both in vitro and in vivo. This interaction led to CtIP degradation by the ubiquitin–proteasome pathway. As expected, SIAH-1 induced p21Waf−1/Cip−1 transcription in Jurkat-T cell. Surprisingly, a SIAH protein deleted of its RING finger, SIAH-1ΔN, which is able to interact with CtIP but does not promote its degradation, also induced transcription from the p21Waf−1 promoter in a similar extent as did SIAH-1. Our results suggest that p21Waf−1/Cip−1 induction by SIAH-1 could not be mediated by CtIP degradation.
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Acknowledgements
We thank Dr R Baer for the kind gift of CtIP plasmid and anti-CtIP antibodies, Dr. Feunteun for anti-BRCA1 antibodies and Dr Fusco for HA-CtIP plasmid. This work was partially supported by grants from Eli Lilly International Foundation, the ‘ECOS-Sud’ program (action U97S03), the ‘Association pour la Recherche Contre le Cancer (ARC)’ and ‘La Ligue Contre le Cancer’.
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Germani, A., Prabel, A., Mourah, S. et al. SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene 22, 8845–8851 (2003). https://doi.org/10.1038/sj.onc.1206994
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DOI: https://doi.org/10.1038/sj.onc.1206994
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