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.
Irvin
Brenda J
BJ
Department of Biochemistry, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Preston Research Building, 23rd and Pierce, Nashville, TN 37232, USA.
Wood
Lauren D
LD
Wang
Lilin
L
Fenrick
Randy
R
Sansam
Courtney G
CG
Packham
Graham
G
Kinch
Michael
M
Yang
Elizabeth
E
Hiebert
Scott W
SW
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D051020:bcl-X Protein; D000097764:ETS Translocation Variant 6 Protein
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D000097764:ETS Translocation Variant 6 Protein; C494812:Bcl2l1 protein, mouse