A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2.
Ectopic expression of LIM-only protein 2 (LMO2) in T-cells, as a result of chromosomal translocations or retroviral insertion, plays an important role in the onset of T-cell leukemias. Two transcripts of LMO2 gene (LMO2-a and LMO2-b) have been reported to encode a same 158-amino-acid protein. We have previously reported a novel transcript of human LMO2 gene (LMO2-c) encoding a 151-amino-acid protein, and defined its promoter region. In the present study, we investigated the regulation of the LMO2-c expression and the functions of LMO2-c. We found that LMO2-c expression is regulated by the cooperation of two essential hematopoietic transcription factors GATA-1 and PU.1 in various hematopoietic cell lines, suggesting an important functional role for LMO2-c in the hematopoietic system. More importantly, we demonstrated that LMO2-c acts as an antagonist of LMO2-a/b binding to its partners, therefore blocking the transactivation of LMO2-a/b on its target genes. These findings provide novel evidence to the functions of LMO2 gene in the hematopoietic system and leukemia.
Wang
Q
Q
Laboratory of Molecular Medicine, Medical College, Nankai University, Tianjin, PR China.
Zhang
M
M
Wang
X
X
Yuan
W
W
Chen
D
D
Royer-Pokora
B
B
Zhu
T
T
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000502:physiology*; D005786:Gene Expression Regulation; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C085117:LMO2 protein, human