HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 27, 28706-28714, July 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/27/28706    most recent M400376200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fortin, A. Articles by Slack, R. S. Search for Related Content PubMed PubMed Citation Articles by Fortin, A. Articles by Slack, R. S. Social Bookmarking                      What's this?

The Proapoptotic Gene SIVA Is a Direct Transcriptional Target for the Tumor Suppressors p53 and E2F1^*

Andre Fortin, Jason G. MacLaurin, Nicole Arbour, Sean P. Cregan¶, Neena Kushwaha||, Steven M. Callaghan, David S. Park**, Paul R. Albert, and Ruth S. Slack

From the Ottawa Health Research Institute, Neuroscience Centre and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

The p53 tumor suppressor gene is believed to play an important role in neuronal cell death in acute neurological disease and in neurodegeneration. The p53 signaling cascade is complex, and the mechanism by which p53 induces apoptosis is cell type-dependent. Using DNA microarray analysis, we have found a striking induction of the proapoptotic gene, SIVA. SIVA is a proapoptotic protein containing a death domain and interacts with members of the tumor necrosis factor receptor family as well as anti-apoptotic Bcl-2 family proteins. SIVA is induced following direct p53 gene delivery, treatment with a DNA-damaging agent camptothecin, and stroke injury in vivo. SIVA up-regulation is sufficient to initiate the apoptotic cascade in neurons. Through isolation and analysis of the SIVA promoter, we have identified response elements for both p53 and E2F1. Like p53, E2F1 is another tumor suppressor gene involved in the regulation of apoptosis, including neuronal injury models. We have identified E2F consensus sites in the promoter region, whereas p53 recognition sequences were found in intron1. Sequence analysis has shown that these consensus sites are also conserved between mouse and human SIVA genes. Electrophoretic mobility shift assays reveal that both transcription factors are capable of binding to putative consensus sites, and luciferase reporter assays reveal that E2F1 and p53 can activate transcription from the SIVA promoter. Here, we report that the proapoptotic gene, SIVA, which functions in a broad spectrum of cell types, is a direct transcriptional target for both tumor suppressors, p53 and E2F1.

Received for publication, January 13, 2004 , and in revised form, April 1, 2004.

^* This work was supported in part by grants from the Canadian Institutes of Health Research (CIHR) and Heart and Stroke Foundation of Ontario (to R. S. S.). Adenoviral vectors were generated by the Viral Vector Core Facility supported by grants from the Canadian Stroke Network (to R. S. S. and D. S. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Canadian Stroke Network.

Supported by an Ontario Neurotrauma studentship.

^¶ Supported by a CIHR postdoctoral fellowship. Current address: Robarts Research Institute, Cell Biology Group, P. O. Box 5015, 100 Perth Dr., London, Ontario N6A 5K8, Canada.

^|| Supported by a CIHR studentship.

^** A CIHR/Novartis Chair in Neuroscience.

A GlaxoSmithKline professor.

To whom correspondence should be addressed: Ottawa Health Research Institute, University of Ottawa, 451 Smyth Rd., Ottawa, Ontario K1H 8M5, Canada. Tel.: 613-562-5800 (ext. 8459); Fax: 613-562-5403; E-mail: rslack{at}uottawa.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F.-T. Lin, Y.-J. Lai, N. Makarova, G. Tigyi, and W.-C. Lin The Lysophosphatidic Acid 2 Receptor Mediates Down-regulation of Siva-1 to Promote Cell Survival J. Biol. Chem., December 28, 2007; 282(52): 37759 - 37769. [Abstract] [Full Text] [PDF]

				J. L. Vanderluit, C. A. Wylie, K. A. McClellan, N. Ghanem, A. Fortin, S. Callaghan, J. G. MacLaurin, D. S. Park, and R. S. Slack The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate J. Cell Biol., October 3, 2007; 178(1): 129 - 139. [Abstract] [Full Text] [PDF]

				T. Subramanian, S. Vijayalingam, E. Lomonosova, L.-j. Zhao, and G. Chinnadurai Evidence for Involvement of BH3-Only Proapoptotic Members in Adenovirus-Induced Apoptosis J. Virol., October 1, 2007; 81(19): 10486 - 10495. [Abstract] [Full Text] [PDF]

				K. L.M. Boylan, M. A. Gosse, S. E. Staggs, S. Janz, S. Grindle, G. S. Kansas, and B. G. Van Ness A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma Cancer Res., May 1, 2007; 67(9): 4069 - 4078. [Abstract] [Full Text] [PDF]

				G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. [Abstract] [Full Text] [PDF]

				M. Lucerna, J. Pomyje, D. Mechtcheriakova, A. Kadl, F. Gruber, M. Bilban, Y. Sobanov, G. Schabbauer, J. Breuss, O. Wagner, et al. Sustained Expression of Early Growth Response Protein-1 Blocks Angiogenesis and Tumor Growth. Cancer Res., July 1, 2006; 66(13): 6708 - 6713. [Abstract] [Full Text] [PDF]

				F. Chu, J. Barkinge, S. Hawkins, R. Gudi, R. Salgia, and P. V.S. Kanteti Expression of Siva-1 Protein or Its Putative Amphipathic Helical Region Enhances Cisplatin-Induced Apoptosis in Breast Cancer Cells: Effect of Elevated Levels of BCL-2 Cancer Res., June 15, 2005; 65(12): 5301 - 5309. [Abstract] [Full Text] [PDF]