The Myc/Max/Mad Network and the Transcriptional Control of Cell Behavior
Abstract
The Myc/Max/Mad network comprises a group of transcription factors whose distinct interactions result in gene-specific transcriptional activation or repression. A great deal of research indicates that the functions of the network play roles in cell proliferation, differentiation, and death. In this review we focus on the Myc and Mad protein families and attempt to relate their biological functions to their transcriptional activities and gene targets. Both Myc and Mad, as well as the more recently described Mnt and Mga proteins, form heterodimers with Max, permitting binding to specific DNA sequences. These DNA-bound heterodimers recruit coactivator or corepressor complexes that generate alterations in chromatin structure, which in turn modulate transcription. Initial identification of target genes suggests that the network regulates genes involved in the cell cycle, growth, life span, and morphology. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.
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MAX binds to DNA as a dimer and facilitates cooperative activity with a range of partners.
“MAX canonically recognizes a short, common sequence (the domain CACGTG), but its structure leads it to bind to DNA as a dimer, and facilitates cooperative activity with a range of partners (Grandori et al., 2000) with many weaker and longer-range sequence determinants of binding (Allevato et al., 2017).”
From WILDS: A Benchmark of in-the-Wild Distribution Shifts (2020) · cites this paper as Grandori et al., 2000
MAX canonically recognizes a short, common sequence (the domain CACGTG).
“MAX canonically recognizes a short, common sequence (the domain CACGTG), but its structure leads it to bind to DNA as a dimer, and facilitates cooperative activity with a range of partners (Grandori et al., 2000) with many weaker and longer-range sequence determinants of binding (Allevato et al., 2017).”
From WILDS: A Benchmark of in-the-Wild Distribution Shifts (2020) · cites this paper as Grandori et al., 2000
Net-like is most similar to the Drosophila bHLH transcriptional repressor Net at 35% identity and almost equally similar to members of the Myc and Max families.
“When compared to the databases, the Net-like protein is most similar to the Drosophila bHLH transcriptional repressor Net (35% identity; Brentrup et al., 2000) and almost equally similar to the members of the Myc and Max families”
From Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish (2003) · cites this paper as Grandori et al., 2000
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- Authors
- Grandori, C., Cowley, S. M., James, L. P., & Eisenman, R. N.
- Affiliations
- University of Washington (US)
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 2000-11
- Volume
- 16
- Issue
- 1
- Pages
- 653-699
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- OpenAlex
- W2149357952
- Cited by
- 1,333
- References
- 10
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 29 · 2023: 63 · 2022: 53 · 2021: 45 · 2020: 35 · 2019: 29 · 2018: 38 · 2017: 48 · 2016: 31 · 2015: 36 · 2014: 46 · 2013: 51 · 2012: 53
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ca075125-05)
- National Cancer Institute (R29CA75125, R01CA057138, R01CA020525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Myc proteins, Mad proteins, Max protein, transcription factors, heterodimerization, coactivator complexes, corepressor complex, chromatin structure, transcriptional regulation, cell proliferation, cell differentiation, cell death, cell cycle, lifespan, cell morphology, signaling pathways
- MeSH terms
- Animals, DNA-Binding Proteins, Humans, Repressor Proteins, Transcription Factors, Proto-Oncogene Proteins c-myc, Oncogene Protein p55(v-myc), Helix-Loop-Helix Motifs, Basic-Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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