Association of a novel GTP binding protein, DRG, with TAL oncogenic proteins.
TAL1 is a basic helix-loop-helix (bHLH) protein involved in hematopoietic development. In T cell acute lymphoblastic leukemic cells, TAL1 is aberrantly overexpressed and is thought to contribute to oncogenesis. To identify proteins that interact with TAL1 in mediating leukemogenesis, we used TAL1 as a bait in a two-hybrid interaction screen, and isolated a cDNA clone that encodes a unique GTP binding protein, DRG. The interaction between DRG and TAL1 was confirmed both in vitro and in vivo. DRG was also shown to bind in vitro to two TAL1-related proteins, TAL2 and Lyl1. Mutational analyses showed that the HLH domain of TAL1 was necessary and sufficient for its interaction with the C-terminus of DRG. Furthermore, while DRG and E47 compete to interact with TAL1, TAL1 binds to DRG and E47 in a mutually exclusive manner. In rat embryonic fibroblast transformation assays, DRG stimulated the cotransforming activity of c-myc and ras. Based on these results, DRG appears to be a potential target for TAL-like oncoproteins.
Mahajan
M A
MA
Department of Cell Biology, New York University Medical Center, New York, NY 10016, USA.
Park
S T
ST
Sun
X H
XH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D018631:ras Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D051820:TCF Transcription Factors; C553060:Tcf7l1 protein, rat; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C078418:developmentally regulated GTP-binding protein; D019204:GTP-Binding Proteins; D018631:ras Proteins