Preferential expression of HMGI-C isoforms lacking the acidic carboxy terminal in human leukemia.
The high mobility group HMGI chromosomal proteins are an important component of chromatin. The HMGI-C protein consists of three amino terminal DNA binding domains ("AT hooks"), a linker region and an acidic carboxy domain. In mesenchymal tumors, chromosomal translocations of 12q13-15 result in fusion proteins containing the AT hooks and novel carboxy terminals. We have investigated the status of the HMGI-C gene in two cases of leukemia with anomalies of chromosome 12q and identified three novel isoforms (designated alpha, beta and gamma) derived from alternate splicing. One of the patients expressed all three isoforms, whereas the second patient expressed only the gamma isoform; preferential expression of the HMGI-C gamma isoform was also detected in the leukemic cell lines ML3 and BV173. The results are consistent with a crucial role for truncation of the acidic carboxy domain of HMGI-C in abnormal growth.
Kottickal
L V
LV
Department of Molecular Hematology and Therapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Sarada
B
B
Ashar
H
H
Chada
K
K
Nagarajan
L
L
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007938:Leukemia / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D012333:RNA, Messenger