NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells.
We recently showed that a subset of human T acute lymphoblastic leukemia (T-ALL) cell lines expresses low basal levels of p50, a nuclear factor-kappaB (NF-kappaB)/Rel family member, resulting in their capacity to activate the atypical p65:cRel complex rather than the classic p50:p65 dimer. Here, we show that the transcription factor TAL1 (also known as SCL) binds to the promoter of the NFKB1 gene that encodes p50 and represses its transcription to set up this unique response in T-ALL cells. When TAL1 expression is reduced in CEM T leukemia cells, basal NFKB1 expression is increased, and the levels of p65:cRel complex and transcription of its target gene, such as intercellular adhesion molecule-1 (ICAM-1), are reduced in response to etoposide treatment. Moreover, a significant negative correlation between NFKB1 and TAL1 or LMO1 was found in primary human TAL1/LMO1 double-positive T-ALL samples previously described by Ferrando et al. Thus, TAL1 modulates NFKB1 expression and an NF-kappaB-dependent transcriptional program in a subset of human T-cell leukemia cells.
Chang
Pei-Yun
PY
Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Draheim
Kyle
K
Kelliher
Michelle A
MA
Miyamoto
Shigeki
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D052002:NF-kappa B p50 Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D005047:Etoposide; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051996:Transcription Factor RelA; C489548:NFKB1 protein, human; C067143:TAL1 protein, human