Cited by 551Genomics and Chromatin DynamicsProtein Structure and DynamicsEnzyme Structure and Function

X-Ray Structures of Myc-Max and Mad-Max Recognizing DNA

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Nair, Satish K., Burley, Stephen K.·2003·Cell

Abstract

X-ray structures of the basic/helix-loop-helix/leucine zipper (bHLHZ) domains of Myc-Max and Mad-Max heterodimers bound to their common DNA target (Enhancer or E box hexanucleotide, 5'-CACGTG-3') have been determined at 1.9 A and 2.0 A resolution, respectively. E box recognition by these two structurally similar transcription factor pairs determines whether a cell will divide and proliferate (Myc-Max) or differentiate and become quiescent (Mad-Max). Deregulation of Myc has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. Both quasisymmetric heterodimers resemble the symmetric Max homodimer, albeit with marked structural differences in the coiled-coil leucine zipper regions that explain preferential homo- and heteromeric dimerization of these three evolutionarily related DNA-binding proteins. The Myc-Max heterodimer, but not its Mad-Max counterpart, dimerizes to form a bivalent heterotetramer, which explains how Myc can upregulate expression of genes with promoters bearing widely separated E boxes.

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Crossref · 10.1016/s0092-8674(02)01284-9

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  • The Myc/Max family DNA-binding site (E-box, 5'-CACGTG-3') encompasses the core sequence 5'-CGTG-3', which is also present in the HIF-1 consensus sequence and is part of the sequence specificity of NSC-13502.

    “One example is the Myc/ Max family of transcription factors, whose DNA-binding site (E-box, 5V-CACGTG-3V; ref. 46) encompasses the core sequence 5V-CGTG-3V, which is also present in the HIF-1 consensus sequence and is part of the sequence specificity of NSC-13502.”

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Authors
Nair, S. K., & Burley, S. K.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Burley, Stephen K.
Venue
Cell
Publisher
Elsevier BV
Published
2003-01
Volume
112
Issue
2
Pages
193-205
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2104538433
Cited by
551
References
70
Citations by year
2026: 21 · 2025: 34 · 2024: 37 · 2023: 38 · 2022: 28 · 2021: 31 · 2020: 22 · 2019: 33 · 2018: 24 · 2017: 27 · 2016: 13 · 2015: 25 · 2014: 33 · 2013: 20 · 2012: 25
FWCI
7.58
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
Myc-Max heterodimer, bHLH-Zip transcription factors, Burkitt lymphoma, neuroblastoma, small cell lung cancer
MeSH terms
Amino Acid Sequence, Base Sequence, Crystallization, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Repressor Proteins, Structure-Activity Relationship, Transcription Factors, Proto-Oncogene Proteins c-myc, Leucine Zippers, Crystallography, X-Ray, Dimerization, Protein Structure, Quaternary, E-Box Elements, Basic-Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

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