Mmip-2, a novel RING finger protein that interacts with mad members of the Myc oncoprotein network

• Published in: Oncogene Vol. 18; no. 48; pp. 6621 - 6634
• Main Authors: YIN, X.-Y, GUPTA, K, WEI PING HAN, LEVITAN, E. S, PROCHOWNIK, E. V
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 18.11.1999; Nature Publishing Group
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Base Sequence; Binding sites; Biological and medical sciences; c-Myc protein; Carrier Proteins; Cell Cycle Proteins; Cloning, Molecular; Deoxyribonucleic acid; DNA; DNA, Complementary; Fibroblasts; Fundamental and applied biological sciences. Psychology; Fungal Proteins - metabolism; Green fluorescent protein; Leucine zipper proteins; Mad protein; Mice; Mmip-2 protein; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Myc protein; Nuclear Proteins - metabolism; Oncoproteins; Phosphoproteins - metabolism; Precipitin Tests; Protein Binding; Proteins; Proto-Oncogene Proteins c-myc - metabolism; Repressor Proteins; RING finger proteins; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Subcellular Fractions - metabolism; Transcription; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Two-Hybrid System Techniques; ZIP protein; Vertebrata; Regulation(control); Mammalia; Cell function; Mouse; Transcription; C-Onc gene; Rodentia; Molecular interaction; Transcription factor; Localization
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203097

Mad proteins are basic-helix-loop-helix-leucine zipper (bHLH-ZIP)-containing members of the myc oncoprotein network. They interact with the bHLH-ZIP protein max, compete for the same DNA binding sites as myc-max heterodimers and down-regulate myc-responsive genes. Using the bHLH-ZIP domain of mad1 as a yeast two-hybrid 'bait', we identified Mmip-2, a novel RING finger protein that interacts with all mad members, but weakly or not at all with c-myc, max or unrelated bHLH or bZIP proteins. The mad1-Mmip-2 interaction is mediated by the ZIP domain in the former protein and by at least two regions in the latter which do not include the RING finger. Mmip-2 can disrupt max-mad DNA binding and can reverse the suppressive effects of mad proteins on c-myc-responsive target genes and on c-myc + ras-mediated focus formation in fibroblasts. Tagging with spectral variants of green fluorescent protein showed that Mmip-2 and mad proteins reside in separate cytoplasmic and nuclear compartments, respectively. When co-expressed, however, the proteins interact and translocate to the cellular compartment occupied by the more abundant protein. These observations suggest a novel way by which Mmip-2 can modulate the transcriptional activity of myc oncoproteins.