myc, max, and a novel rlf-L-myc fusion protein in small-cell lung cancer.
The functional properties of Myc proteins are likely to be modulated by interactions with other nuclear proteins. One such protein called Max has already been characterized (1). Through their homologous helix-loop-helix and leucine zipper structures, Myc and Max proteins form heterodimers that bind to specific DNA sequences more efficiently than Myc or Max alone. We have recently identified delta Max, a naturally occurring truncated version of Max, which is also able to dimerize with Myc in the nucleus, but is cytoplasmic in the absence of Myc. These two forms of Max can act either as enhancers or suppressors of cotransformation by c-myc and ras. Oncogenic activation of myc genes in human cancer involves deregulated myc expression. Oncogenes of the myc family are activated in several types of human tumors as a result of gene amplification or chromosomal translocation. We have recently characterized a gene fusion and a chimeric protein product formed by L-myc and part of a novel gene called rlf in small-cell lung cancer (SCLC) cell lines. Although the chimeric mRNAs were shown to be identical, they result from distinct DNA rearrangements. We have also established a physical linkage between normal rlf and L-myc using pulsed field gel electrophoresis. Thus, the rlf-L-myc gene fusions are due to similar but not identical intrachromosomal rearrangements at 1p32. Similar in vivo rearrangements involving rlf and L-myc have been found in at least one primary SCLC tumor. The presence of independent genetic lesions that cause the formation of identical chimeric rlf-L-myc proteins suggests a role for the fusion protein in the development of these SCLC tumors.
Västrik
I
I
Department of Virology and Pathology, University of Helsinki, Finland.
Mäkelä
T P
TP
Koskinen
P J
PJ
Saksela
K
K
Alitalo
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D018288:Carcinoma, Small Cell / Q000209:etiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005784:Gene Amplification; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014760:Viral Fusion Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C067850:Myc associated factor X; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D014760:Viral Fusion Proteins; C073593:rlf-L-myc fusion protein, human