A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias.
Translocations involving chromosome band 11q23 in acute leukemias have recently been shown to involve the HRX gene that codes for a protein with significant similarity to Drosophila trithorax. HRX gene alterations are consistently observed in t(4;11) (q21;q23)-carrying leukemias and cell lines by Southern blot analyses and are accompanied by HRX transcripts of anomalous size on Northern blots. HRX-homologous cDNAs were isolated from a library prepared from t(4;11)-carrying acute leukemia cells. cDNAs representative of transcription products from the derivative 11 chromosome were shown to contain HRX sequences fused to sequences derived from chromosome band 4q21. Fragments of the latter were used to clone and analyze cDNAs for wild-type 4q21 transcripts that predicted a 140-Kd basic protein (named FEL) that is rich in prolines, serines, and charged amino acids. FEL contains guanosine triphosphate-binding and nuclear localization consensus sequences and uses one of two possible 5' exons encoding the first 12 or 5 amino acids. After t(4;11) translocations, 913 C-terminal amino acids of FEL are fused in frame to the N-terminal portion of HRX containing its minor groove DNA binding motifs. These features are similar to predicted t(11;19) fusion proteins, suggesting that HRX consistently contributes a novel DNA-binding motif to at least two different chimeric proteins in acute leukemias.
Morrissey
J
J
Department of Pathology, Stanford University School of Medicine, CA 94305-5324.
Tkachuk
D C
DC
Milatovich
A
A
Francke
U
U
Link
M
M
Cleary
M L
ML
D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011392:Proline / Q000032:analysis; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012694:Serine / Q000032:analysis; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D012694:Serine; D011392:Proline; D011495:Histone-Lysine N-Methyltransferase