The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL).
The TTG-2 gene has been identified at the site of chromosomal translocations in acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and 30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these translocation breakpoints in the deregulation of TTG-2 in T-ALL we have determined the complete structure of this gene. Isolation of new TTG-2 cDNA clones from fetal liver identified an alternative transcript (TTG-2a) containing two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6 exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from promoter 2 (P2) differ in the length of the 5' untranslated region, but encode the same protein. A high level of TTG-2a was present in fetal liver and spleen, whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was found. The transcription start site for TTG-2a was identified by RNase protection experiments and it displayed sequence homology to an initiator element (inr). P1 lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new genomic organisation revealed that all known chromosomal translocations map upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2 intact. These results show that chromosomal translocations disrupt the TTG-2 gene itself, further confirming its role in the development of T-ALL.
Royer-Pokora
B
B
Institute of Human Genetics, University of Heidelberg, Germany.
Rogers
M
M
Zhu
T H
TH
Schneider
S
S
Loos
U
U
Bölitz
U
U
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns; D060588:LIM Domain Proteins; D015458:Leukemia, T-Cell / Q000235:genetics*; D008667:Metalloproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm