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

Oncogene volume 22, pages 8845–8851 (2003)Cite this article

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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References

  • Antonio C, Ferby I, Wilhelm H, Jones M, Karsenti E, Nebreda AR and Vernos I . (2000). Cell, 102, 425–435.

  • Boehm J, He Y, Greiner A, Staudt L and Wirth T . (2001). EMBO J., 20, 4153–4162.

  • Bruzzoni-Giovanelli H, Faille A, Linares-Cruz G, Nemani M, Le Deist F, Germani A, Chassoux D, Millot G, Roperch JP, Amson R, Telerman A and Calvo F . (1999). Oncogene, 18, 7101–7109.

  • Chen Y, Lee WH and Chew HK . (1999). J. Cell. Physiol., 181, 385–392.

  • Funabiki H and Murray AW . (2000). Cell, 102, 411–424.

  • Germani A, Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N and Calvo F . (2000). Oncogene, 19, 5997–6006.

  • Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S and Varin-Blank N . (1999). Mol. Cell. Biol., 19, 3798–3807.

  • Koipally J and Georgopoulos K . (2002). J. Biol. Chem., 277, 23143–23149.

  • Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD and Lee WH . (1999). J. Biol. Chem., 274, 11334–11338.

  • Li S, Li Y, Carthew RW and Lai ZC . (1997). Cell, 90, 469–478.

  • Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY and Lee WH . (2000). Nature, 406, 210–215.

  • Linares-Cruz G, Bruzzoni-Giovanelli H, Alvaro V, Roperch JP, Tuynder M, Schoevaert D, Nemani M, Prieur S, Lethrosne F, Piouffre L, Reclar V, Faille A, Chassoux D, Dausset J, Amson RB, Calvo F and Telerman A . (1998). Proc. Natl. Acad. Sci. USA, 95, 1131–1135.

  • Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, White RL and Matsunami N . (2001). Mol. Cell, 7, 927–936.

  • Matsuzawa S, Li C, Ni CZ, Takayama S, Reed JC and Ely KR . (2003). J. Biol. Chem., 278, 1837–1840.

  • Matsuzawa SI and Reed JC . (2001). Mol. Cell, 7, 915–926.

  • Meloni AR, Smith EJ and Nevins JR . (1999). Proc. Natl. Acad. Sci. USA, 96, 9574–9579.

  • Nemani M, Linares-Cruz G, Bruzzoni-Giovanelli H, Roperch JP, Tuynder M, Bougueleret L, Cherif D, Medhioub M, Pasturaud P, Alvaro V, der Sarkissan H, Cazes L, Le Paslier D, Le Gall I, Israeli D, Dausset J, Sigaux F, Chumakov I, Oren M, Calvo F, Amson RB, Cohen D and Telerman A . (1996). Proc. Natl. Acad. Sci. USA, 93, 9039–9042.

  • Polekhina G, House CM, Traficante N, Mackay JP, Relaix F, Sassoon DA, Parker MW and Bowtell DD . (2002). Nat. Struct. Biol., 9, 68–75.

  • Schaeper U, Subramanian T, Lim L, Boyd JM and Chinnadurai G . (1998). J. Biol. Chem., 273, 8549–8552.

  • Tang AH, Neufeld TP, Kwan E and Rubin GM . (1997). Cell, 90, 459–467.

  • Tiedt R, Bartholdy BA, Matthias G, Newell JW and Matthias P . (2001). EMBO J., 20, 4143–4152.

  • Wheeler TC, Chin LS, Li Y, Roudabush FL and Li L . (2002). J. Biol. Chem., 277, 10273–10282.

  • Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH and Bartel PL . (1998). Oncogene, 17, 2279–2285.

  • Wu-Baer F and Baer R . (2001). Nature, 414, 36.

  • Yu X, Wu LC, Bowcock AM, Aronheim A and Baer R . (1998). J. Biol. Chem., 273, 25388–25392.

  • Zhang J, Guenther MG, Carthew RW and Lazar MA . (1998). Genes Dev., 12, 1775–1780.

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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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Authors and Affiliations

  1. Laboratory of Vascular Biology and Gene Therapy, Centro Cardiologico Fondazione ‘I. Monzino’-IRCCS, Via Parea 4, Milano, 20138, Italy

    Antonia Germani & Anna Di Carlo

  2. Département d'Hématologie de l'Institut Cochin INSERM U567 UMR CNRS 8104 ParisV, Hôpital Cochin, 27 rue Faubourg Saint Jacques, Paris, 75014, France

    Antonia Germani, Sylvie Gisselbrecht & Nadine Varin-Blank

  3. Laboratoire de Pharmacologie Expérimentale et Clinique INSERM EMI-0334, Institut de Génétique Moléculaire, Hôpital Saint-Louis, 27 rue Juliette Dodu, Paris, 75010, France

    Audrey Prabel, Samia Mourah, Marie-Pierre Podgorniak, Fabien Calvo & Heriberto Bruzzoni-Giovanelli

  4. Sección Bioquímica, Facultad de Ciencias, Iguá 4225, Montevideo, Uruguay

    Ricardo Ehrlich

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  1. Antonia Germani
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  2. Audrey Prabel
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Correspondence to Heriberto Bruzzoni-Giovanelli.

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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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