The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for vertebrate MAD and MAX

• Published in: Oncogene Vol. 17; no. 9; pp. 1109 - 1118
• Main Authors: YUAN, J, TIRABASSI, R. S, BUSH, A. B, COLE, M. D
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 03.09.1998; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic-Leucine Zipper Transcription Factors; Binding Sites - genetics; Biological and medical sciences; c-Myc protein; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins; Cell cycle; Cell cycle, cell proliferation; Cell differentiation; Cell physiology; Cell proliferation; Cell Transformation, Neoplastic - genetics; Deoxyribonucleic acid; Developmental stages; Dimerization; DNA; DNA - metabolism; DNA, Complementary - chemistry; DNA, Complementary - genetics; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Embryo fibroblasts; Embryogenesis; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genes, Helminth - genetics; Genes, myc - genetics; Genes, ras - genetics; Genes, Tumor Suppressor - genetics; Genetic transformation; Helminth Proteins - chemistry; Helminth Proteins - genetics; Helminth Proteins - metabolism; Intestine; Intestines - cytology; Intestines - metabolism; Larva - genetics; Larva - metabolism; MAD protein; Mitosis - genetics; Molecular and cellular biology; Molecular Sequence Data; Myc protein; Neurons - metabolism; Nucleotide sequence; Protein Binding; Protein Structure, Tertiary; Rats; Repressor Proteins; Sequence Alignment; Sequence Analysis, DNA; Transcription Factors - metabolism; Vertebrates - genetics; Vertebrates - physiology; Cell proliferation; Nucleotide sequence; Homology; Molecular interaction; Cell differentiation; Gene expression; Heterodimer; Caenorhabditis elegans; Signal transduction; Regulation(control); Gene; Helmintha; Development; Nemathelminthia; Invertebrata; Transcription factor; Nematoda
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1202036

The genes of the myc/max/mad family play an important role in controlling cell proliferation and differentiation. We have identified the first homologues of the mad and max genes in the nematode C. elegans, which we have named mdl-1 and mxl-1 respectively. Like the vertebrate MAD proteins, MDL-1 binds an E-box DNA sequence (CACGTG) when dimerized with MXL-1. However, unlike vertebrate MAX, MXL-1 can not form homodimers and bind to DNA alone. Promoter fusions to a GFP reporter suggest that these genes are coexpressed in posterior intestinal and post-mitotic neuronal cells during larval development. The coexpression in the posterior intestinal cells occurs before their final division at the end of the L1 stage and persists afterwards, demonstrating that mad and max expression can be correlated directly to the cell cycle state of an individual cell type. These data also show that mxl-1 is an obligate partner for mdl-1 in vivo and in vitro and indicate that these genes may play an important role in post-embryonic development. Finally, MDL-1 can suppress activated c-MYC/RAS-induced focus formation in a rat embryo fibroblast transformation assay. Like the vertebrate MAD protein, MDL-1 activity in suppressing transformation is dependent on a functional SIN3 interaction domain.