Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (435K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (35)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Janz, A.
Right arrow Articles by Thomas-Tikhonenko, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Janz, A.
Right arrow Articles by Thomas-Tikhonenko, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 11 2268-2275
© 2000 Oxford University Press

Activation of the Myc oncoprotein leads to increased turnover of thrombospondin-1 mRNA

Annette Janz1,2, Cinzia Sevignani3, Karla Kenyon2, Cam V. Ngo3 and Andrei Thomas-Tikhonenko2,3,*

1Technische Universität Braunschweig, D-38023 Braunschweig, Germany, 2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA and 3Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA

The Myc oncoprotein is implicated in transcriptional regulation of a variety of genes pertaining to cell cycle and neoplastic transformation. Examples of both positive and negative regulation have been reported that involve E-box and initiator (Inr) promoter elements, respectively. In both cases, Myc is thought to induce changes in transcription initiation. We have previously shown that overexpression of Myc causes down-regulation of the thrombospondin-1 (tsp-1) gene, an important negative modulator of tumor angiogenesis. In this study, we demonstrate that Myc in combination with Max can bind, albeit with low affinity, to an E-box-like element in the tsp-1 promoter. However, the 2.7 kb DNA segment containing both this non-canonical E-box and an Inr-like sequence does not constitute a Myc-responsive element in a transient expression system. Furthermore, Myc does not significantly affect the rate of initiation or elongation of the tsp-1 mRNA. Thus, in this instance Myc does not act as a canonical transcription factor. Instead, as demonstrated by blocking de novo RNA synthesis, down-regulation of the tsp-1 gene by Myc occurs through increased mRNA turnover. To our knowledge, this is the first example of gene regulation by Myc that involves mRNA destabilization.

* To whom correspondence should be addressed at: Department of Pathobiology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6051, USA. Tel: +1 215 573 5138; Fax: +1 215 898 0719; Email: andreit@vet.upenn.edu Present address: Annette Janz, GSF-Haematologikum, Institut für Klinische Molekularbiologie, D-81377 München, Germany


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S.-Y. Kang, O. J. Halvorsen, K. Gravdal, N. Bhattacharya, J. M. Lee, N. W. Liu, B. T. Johnston, A. B. Johnston, S. A. Haukaas, K. Aamodt, et al.
Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1
PNAS, July 21, 2009; 106(29): 12115 - 12120.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Potikyan, R. O.V. Savene, J. M. Gaulden, K. A. France, Z. Zhou, E. S. Kleinerman, S. L. Lessnick, and C. T. Denny
EWS/FLI1 Regulates Tumor Angiogenesis in Ewing's Sarcoma via Suppression of Thrombospondins
Cancer Res., July 15, 2007; 67(14): 6675 - 6684.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Giuriato, S. Ryeom, A. C. Fan, P. Bachireddy, R. C. Lynch, M. J. Rioth, J. van Riggelen, A. M. Kopelman, E. Passegue, F. Tang, et al.
Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch
PNAS, October 31, 2006; 103(44): 16266 - 16271.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
K. Shchors, E. Shchors, F. Rostker, E. R. Lawlor, L. Brown-Swigart, and G. I. Evan
The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta
Genes & Dev., September 15, 2006; 20(18): 2527 - 2538.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
U. E. Knies-Bamforth, S. B. Fox, R. Poulsom, G. I. Evan, and A. L. Harris
c-Myc Interacts with Hypoxia to Induce Angiogenesis In vivo by a Vascular Endothelial Growth Factor-Dependent Mechanism
Cancer Res., September 15, 2004; 64(18): 6563 - 6570.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Thomas-Tikhonenko, I. Viard-Leveugle, M. Dews, P. Wehrli, C. Sevignani, D. Yu, S. Ricci, W. el-Deiry, B. Aronow, G. Kaya, et al.
Myc-Transformed Epithelial Cells Down-Regulate Clusterin, Which Inhibits Their Growth in Vitro and Carcinogenesis in Vivo
Cancer Res., May 1, 2004; 64(9): 3126 - 3136.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.