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

  • Irvin BJ, Wood LD, Wang L, Fenrick R, Sansam CG, Packham G, Kinch M, Yang E, Hiebert SW. TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL. The Journal of biological chemistry. 2003 Nov 21;278(47). 46378-86. PMID: 12960174 [PubMed].

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.