TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL


Irvin, Brenda J., Wood, Lauren D., Wang, Lilin, Fenrick, Randy, Sansam, Courtney G., Packham, Graham, Kinch, Michael, Yang, Elizabeth and Hiebert, Scott W. (2003) TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL. Journal of Biological Chemistry, 278, (47), 46378-46386. (doi:10.1074/jbc.M305189200).

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Original Publication URL: http://dx.doi.org/10.1074/jbc.M305189200

Description/Abstract

The ETS family transcriptional repressor TEL is frequently disrupted by chromosomal translocations, including the t(12;21) in which the second allele of TEL is deleted in up to 90% of the cases. Consistent with its role as a putative tumor suppressor, TEL expression inhibits colony formation by Ras-transformed NIH 3T3 cells and hinders proliferation of a variety of cell types. Although we observed no alteration in the cell cycle of TEL-expressing cells, we did find a marked increase in apoptosis of serum-starved TEL-expressing NIH 3T3 cells. This decrease in cell survival required the DNA binding domain of TEL, suggesting that TEL repressed an anti-apoptotic gene. These observations prompted us to search for genes regulated by ETS family proteins that regulate apoptosis. The anti-apoptotic molecule Bcl-XL contains multiple ets-factor binding sites within its promoters, and TEL repressed a Bcl-XL promoter-linked reporter gene. Moreover, the enforced expression of TEL decreased the endogenous expression of both Bcl-XL mRNA and protein. TEL-mediated repression of Bcl-XL likely affects cell survival via regulation of the apoptotic pathway.

Item Type: Article
Related URLs:
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
Item ID: 26393
Date Deposited: 19 Apr 2006
Last Modified: 01 Apr 2012 02:35
Contributors: Irvin, Brenda J. (Author)
Wood, Lauren D. (Author)
Wang, Lilin (Author)
Fenrick, Randy (Author)
Sansam, Courtney G. (Author)
Packham, Graham (Author)
Kinch, Michael (Author)
Yang, Elizabeth (Author)
Hiebert, Scott W. (Author)
Date: 2003
Status: Published
Contact Email Address: scott.hiebert@mcmail.vanderbilt.edu.
URI: http://eprints.soton.ac.uk/id/eprint/26393

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