Ctip
SIAH-1
and SIAH-2 are the human members of an evolutionary highly conserved E3 ligase family. SIAH-1 is a p53 and p21(Waf-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 p21(Waf-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 p21(Waf-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 p21(Waf-1/Cip-1) transcription in Jurkat-T cell. Surprisingly, a SIAH protein deleted of its
RING finger, SIAH-1DeltaN, which is able to interact with CtIP
but does not promote its degradation, also induced transcription from the p21(Waf-1) promoter in a similar extent as did SIAH-1. Our
results suggest that p21(Waf-1/Cip-1) induction by
SIAH-1 could not be mediated by CtIP degradation.
PMID: 14654780 [PubMed - indexed for MEDLINE]