B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50

• Published in: Cell Vol. 67; no. 6; pp. 1075 - 1087
• Main Authors: Neri, Antonino, Chang, Chih-Chao, Lombardi, Luigia, Salina, Mauro, Corradini, Paolo, Maiolo, Anna T., Chaganti, R.S.K., Dalla-Favera, Riccardo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.12.1991
• Subjects: Amino Acid Sequence; Base Sequence; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 14; Cloning, Molecular; DNA - genetics; DNA-Binding Proteins - genetics; Gene Expression; Gene Rearrangement, B-Lymphocyte, Heavy Chain; genes; Genes, Immunoglobulin; Humans; Immunoglobulin alpha-Chains - genetics; Lymphoma, B-Cell - genetics; Molecular Sequence Data; Multigene Family; NF- Kappa B protein; NF-kappa B - metabolism; Oligodeoxyribonucleotides - chemistry; Oncogenes; Polymerase Chain Reaction; Regulatory Sequences, Nucleic Acid; Restriction Mapping; RNA, Messenger - genetics; Transcription Factors - genetics; Translocation, Genetic; translocations
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(91)90285-7

A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin Cα 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-κB-rel family of transcription factors and carboxy-terminal homology with the NF-κB p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to κB sequences in vitro, although with different specificity from NF-κB p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10- Cα 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds κB 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-κB-rel transcription factors with potential for oncogenic activation in human cancer.