SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Germani A,Prabel A,Mourah S,Podgorniak MP,Di Carlo A,Ehrlich R,Gisselbrecht S,Varin-Blank N,Calvo F,Bruzzoni-Giovanelli H

doi

10.1038/sj.onc.1206994

subject

Has Abstract

pub_date

2003-12-04 00:00:00

pages

8845-51

issue

55

eissn

0950-9232

issn

1476-5594

pii

1206994

journal_volume

22

pub_type

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