Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc

Oncogene
K GuptaE V Prochownik

Abstract

C-myc, a member of the basic helix-loop-helix-leucine zipper (bHLH-ZIP) protein family activates target genes in heterodimeric association with another bHLH-ZIP protein, Max. Max readily homodimerizes, competes with C-myc-Max heterodimers, and represses transcription. Four additional bHLH-ZIP proteins, Mad1, Mxi1, Mad3 and Mad4, heterodimerize with Max and also repress transcription of c-myc-responsive genes. We employed a yeast two-hybid approach to identify proteins which interact with Mxi. We identified a novel ZIP-containing protein, Mmip1 (Mad member-interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc, Max, or with unrelated HLH proteins. The Mmip1-Mxi association is mediated by the ZIP domain of each polypeptide and is as strong or stronger than the associations between c-myc and Max or Max and Mxi1. In vitro, Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive effects of Mad proteins on c-myc functions. Mmipl is found in a variety of cells types, is induced by serum stimulation, and can be co-immunoprecipitated from fibroblasts in association with Mxi1. By interfering with the dimerization between Max and Mad family member proteins, Mmip...Continue Reading

Citations

Dec 4, 2004·Nucleic Acids Research·Kenichi HorisawaHiroshi Yanagawa
Jan 12, 2001·Molecular and Cellular Biology·T A Baudino, J L Cleveland
Oct 14, 2000·Annual Review of Cell and Developmental Biology·C GrandoriR N Eisenman
Mar 6, 2002·British Journal of Pharmacology·Ester VerdaguerAntoni Camins
Mar 23, 2005·Biochemical and Biophysical Research Communications·Chirag A Patel, Giancarlo Ghiselli
May 4, 2016·Genome Biology·Scott M LundbergSu-In Lee
Jun 23, 1999·Oncogene·D Sakamuro, G C Prendergast
Mar 26, 2003·The Journal of Biological Chemistry·Giancarlo GhiselliLinda D Siracusa
May 10, 2000·The Journal of Biological Chemistry·G Ghiselli, R V Iozzo
Aug 11, 2001·Oncogene·X YinE V Prochownik

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