B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50.
A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.
Neri
A
A
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Chang
C C
CC
Lombardi
L
L
Salina
M
M
Corradini
P
P
Maiolo
A T
AT
Chaganti
R S
RS
Dalla-Favera
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D007137:Immunoglobulin alpha-Chains; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA