Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA-binding activity.
The TAL2 gene is activated as a result of the (7;9) (q34;q32) translocation, a chromosome defect found in the malignant cells of some patients with T-cell acute lymphoblastic leukemia (T-ALL). TAL2 potentially encodes a basic helix-loop-helix motif that is highly related to those specified by TAL1 and LYL1, distinct genes that have also been implicated in T-ALL. In this report we show that leukemic cells bearing the (7;9) (q34;q32) translocation express a TAL2 gene product of 108 amino acids. In leukemic cells this product exists in both a phosphorylated (pp13TAL2) and an unphosphorylated (p12TAL2) form. Serine residue 100 is the major site of TAL2 phosphorylation in vivo, and it serves as an effective in vitro substrate for mitogen-activated protein (MAP) kinases such as ERK1. TAL2 polypeptides interact in vivo with the E2A gene products (E47 and E12) to form bHLH heterodimers that bind DNA in a sequence-specific manner. The TAL2 polypeptides do not bind DNA by themselves, however, suggesting that their functional properties may be contingent upon association with other bHLH proteins. Taken together, the properties of TAL2 evaluated here broadly resemble those described previously for TAL1, and therefore support the idea that both proteins promote T-ALL by a common mechanism.
Xia
Y
Y
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Hwang
L Y
LY
Cobb
M H
MH
Baer
R
R
D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C086540:TAL2 protein, human