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

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

(_M_ad_ M_ember-_I_nteracting _P_rotein _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. Mmip1 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, Mmip1 can indirectly up-regulate

the transcriptional activity of c-_MYC_ and suppress the antiproliferative actions of Mad proteins. Access through your institution Buy or subscribe This is a preview of subscription

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TRANSCRIPTION AND CANCER Article 29 June 2021 GFI1 UPREGULATES C-MYC EXPRESSION AND PROMOTES C-MYC-DRIVEN CELL PROLIFERATION Article Open access 13 October 2020 BIOMOLECULAR CONDENSATION OF

NUP98 FUSION PROTEINS DRIVES LEUKEMOGENIC GENE EXPRESSION Article 21 January 2021 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Section of Hematology/Oncology, Childrens Hospital of

Pittsburgh, Pittsburgh, 15213, Pennsylvania, USA Kalpana Gupta, Geetha Anand, Xiaoying Yin, Linette Grove & Edward V Prochownik * The University of Pittsburgh Cancer Institute,

Pittsburgh, 15213, Pennsylvania, USA Geetha Anand, Linette Grove & Edward V Prochownik * The Department of Molecular Genetics and Biochemistry, The University of Pittsburgh Medical

Center, Pittsburgh, 15213, Pennsylvania, USA Linette Grove & Edward V Prochownik Authors * Kalpana Gupta View author publications You can also search for this author inPubMed Google

Scholar * Geetha Anand View author publications You can also search for this author inPubMed Google Scholar * Xiaoying Yin View author publications You can also search for this author

inPubMed Google Scholar * Linette Grove View author publications You can also search for this author inPubMed Google Scholar * Edward V Prochownik View author publications You can also

search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gupta, K., Anand, G., Yin, X. _et al._ Mmip1: a novel

leucine zipper protein that reverses the suppressive effects of Mad family members on c-_MYC_. _Oncogene_ 16, 1149–1159 (1998). https://doi.org/10.1038/sj.onc.1201634 Download citation *

Received: 30 April 1997 * Revised: 10 October 1997 * Accepted: 10 October 1997 * Published: 10 March 1998 * Issue Date: 05 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201634 SHARE THIS

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Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Myc/Mad/leucine * zipper/helix–loop–helix