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

TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL
TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL
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.
0021-9258
46378-46386
Irvin, Brenda J.
bfb8f321-6f86-44ff-98cd-f2dcfb00d15f
Wood, Lauren D.
801d3e9f-bfdf-433f-8614-12d5a5bac8aa
Wang, Lilin
07a3b576-2ffb-4511-8467-9646f1352b4d
Fenrick, Randy
4210a22a-779e-42df-818f-157c939e4b1f
Sansam, Courtney G.
4c77e7a4-9f64-4175-9582-9b7558256581
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Kinch, Michael
534d0ea3-f051-425f-8679-71dc2cdc0282
Yang, Elizabeth
6a17255f-5592-41aa-aab9-7365c2dc48f1
Hiebert, Scott W.
c9251693-6803-44be-ac2b-81ffb27e8e97
Irvin, Brenda J.
bfb8f321-6f86-44ff-98cd-f2dcfb00d15f
Wood, Lauren D.
801d3e9f-bfdf-433f-8614-12d5a5bac8aa
Wang, Lilin
07a3b576-2ffb-4511-8467-9646f1352b4d
Fenrick, Randy
4210a22a-779e-42df-818f-157c939e4b1f
Sansam, Courtney G.
4c77e7a4-9f64-4175-9582-9b7558256581
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Kinch, Michael
534d0ea3-f051-425f-8679-71dc2cdc0282
Yang, Elizabeth
6a17255f-5592-41aa-aab9-7365c2dc48f1
Hiebert, Scott W.
c9251693-6803-44be-ac2b-81ffb27e8e97

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. The Journal of Biological Chemistry, 278 (47), 46378-46386. (doi:10.1074/jbc.M305189200).

Record type: Article

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.

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Published date: 2003

Identifiers

Local EPrints ID: 26393
URI: http://eprints.soton.ac.uk/id/eprint/26393
ISSN: 0021-9258
PURE UUID: 9aaaf6d9-7270-40cb-88df-9a77c6b49fa4
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 19 Apr 2006
Last modified: 16 Mar 2024 03:14

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Contributors

Author: Brenda J. Irvin
Author: Lauren D. Wood
Author: Lilin Wang
Author: Randy Fenrick
Author: Courtney G. Sansam
Author: Graham Packham ORCID iD
Author: Michael Kinch
Author: Elizabeth Yang
Author: Scott W. Hiebert

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