Functional interplay between c‐Myc and Max in B lymphocyte differentiation. (20th August 2018)

• Record Type: Journal Article
• 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
• Is Part Of: EMBO reports. Volume 19:Number 10(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-08-20
• Subjects: B lymphocytes -- cell differentiation -- c‐Myc -- Max -- replication; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201845770
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: 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. 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.