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

• Published in: EMBO reports 2018-10, Vol.19 (10), p.n/a
• Main Authors: Pérez‐Olivares, Mercedes, Trento, Alfonsina, Rodriguez‐Acebes, Sara, González‐Acosta, Daniel, Fernández‐Antorán, David, Román‐García, Sara, Martinez, Dolores, López‐Briones, Tania, Torroja, Carlos, Carrasco, Yolanda R, Méndez, Juan, Moreno de Alborán, Ignacio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence - genetics; Animals; B lymphocytes; B-Lymphocytes - chemistry; B-Lymphocytes - metabolism; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - chemistry; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Biological activity; Cell differentiation; Cell Differentiation - genetics; c‐Myc; Deoxyribonucleic acid; Differentiation (biology); Dimerization; DNA; DNA biosynthesis; DNA Replication - genetics; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; EMBO11; EMBO19; EMBO37; Helix-Loop-Helix Motifs - genetics; Humans; Leucine; Leucine zipper proteins; Leucine Zippers - genetics; Lymphocytes; Lymphocytes B; Max; Mice; Myc protein; Protein Binding - genetics; Proteins; Proto-Oncogene Proteins c-myc - chemistry; Proto-Oncogene Proteins c-myc - genetics; Replication; Scientific Report; Scientific Reports; Transcription factors; Transcriptional Activation - genetics
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201845770

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. Synopsis c‐Myc heterodimerizes with Max to transcriptionally regulate target genes. This study shows that essential biological functions such as proliferation or differentiation can be initiated in the absence of both factors in primary B lymphocytes. B cell progenitors can differentiate in the absence of Myc and Max. DNA replication is impaired in c‐Myc‐deficient B lymphocytes. c‐Myc protein levels are dependent on Max. Max has inhibitory effects in the absence of c‐Myc. Graphical Abstract c‐Myc heterodimerizes with Max to transcriptionally regulate target genes. This study shows that essential biological functions such as proliferation or differentiation can be initiated in the absence of both factors in primary B lymphocytes.