Functional interplay between c-Myc and Max in B lymphocyte differentiation

EMBO Rep. 2018 Oct;19(10):e45770. doi: 10.15252/embr.201845770. Epub 2018 Aug 20.


The Myc family of oncogenic transcription factors regulates myriad cellular functions. Myc proteins contain a basic region/helix-loop-helix/leucine zipper domain that mediates DNA binding and heterodimerization with its partner Max. Among the Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. There is evidence suggesting that c-Myc can perform some of its functions in the absence of Max in different cellular contexts. However, the functional in vivo interplay between c-Myc and Max during B lymphocyte differentiation is not well understood. Using in vivo and ex vivo models, we show that while c-Myc requires Max in primary B lymphocytes, several key biological processes, such as cell differentiation and DNA replication, can initially progress without the formation of c-Myc/Max heterodimers. We also describe that B lymphocytes lacking Myc, Max, or both show upregulation of signaling pathways associated with the B-cell receptor. These data suggest that c-Myc/Max heterodimers are not essential for the initiation of a subset of important biological processes in B lymphocytes, but are required for fine-tuning the initial response after activation.

Keywords: B lymphocytes; Max; cell differentiation; c‐Myc; replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • B-Lymphocytes / chemistry*
  • B-Lymphocytes / metabolism
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Cell Differentiation / genetics*
  • DNA Replication / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Helix-Loop-Helix Motifs / genetics
  • Humans
  • Leucine Zippers / genetics
  • Mice
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / genetics*
  • Transcriptional Activation / genetics


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Max protein, mouse