Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered.

Abstract

We have cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8;14)(q24;qll) translocation, and determined the sequence ofthe MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments ut g a MYC first exon probe demonstrated Hnscriptional deregulation of the MYC gene asated with the T-cell receptor a locus on the 8q + chromosome of SKW-3 cells. Nudeotide sequence analysis of the translocation-aociated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. TheMYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor a locus to a germ-line MYC oncogene results in MYC deregulation.

Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas.

“…The same findings suggest that the observed long-range effect of provirus integration on Myc expression is transmitted in cis. A similar long-range effect on c-myc expression was observed previously in tumors carrying chromosomal translocations involving breakpoints relatively distant from this protooncogene (27)(28)(29)(30). These translocations exert a positive effect on c-myc transcription that is thought to be the result of changes in the chromatin structure in the chromosomal region surrounding the c-myc gene (38).…”

“…The experiments described here were undertaken to determine whether, in addition to the activation ofMlvi-] and Mlvi-4, these provirus insertions also activate Myc. This possibility was suggested by earlier studies showing activation of the human c-myc gene by chromosomal translocation at sites relatively distant from this protooncogene in Burkitt lymphomas (27)(28)(29)(30). The results we present here indeed show that provirus insertions in Mlvi-1 and Mlvi-4 enhance Myc expression.…”

Molecular analysis of a t(14;14) translocation in leukemic T-cells of an ataxia telangiectasia patient.

“…Hybrid 588-AA3 contains the 8q+ chromosome (8pter-* 8q24::14qll-44qter) resulting from the translocation that joins a region containing all of chromosome 14 telomeric to a region -36 kilobases (kb) 5' to the constant (C) region ofthe TCR chain locus (14qll-+l4qter) to a region 3' of c-myc on chromosome 8 (17). No normal chromosome 14 is observed in the parental cell line or in hybrid 588-AA3 (18). These hybrids were used for regional chromosomal localization.…”

Intracellular Pathways Associated with the Etiology of Autism

“…It can phosphorylate factor MYK, which plays a role in cell cycle progression, apoptosis and cellular transformation [18], and it can phosphorylate and activate MNK (interacting protein kinases), which, in turn, phosphorylates cAMP response element-binding protein (CREB). CREB has a well-documented role in neuronal plasticity and long-term memory [19] (Figure 2).…”