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

The Myc proteins (N-, L- and c-Myc) are transcription factors involved in many biological functions such as regulation of cell proliferation, differentiation, metabolism and apoptosis. A large number of human cancers show enhanced expression of myc family proto-oncogenes as one of their hallmarks. These proteins contain a basic region/helix-loop-helix/leucine zipper (bHLHZip) domain that mediates DNA binding and heterodimerization with its partner Max (Myc/Max heterodimer). Among Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. Some reports have implied that c-Myc can perform some functions without Max in different cell contexts. However, the functional interplay in vivo between c-Myc and Max during B lymphocyte differentiation is not well-known. Here we show that c-Myc requires Max. However, key biological processes such as cell differentiation and DNA replication can initially progress without c-Myc/Max heterodimer in primary B lymphocytes. We found that B lymphocytes lacking Myc, Max or both showed upregulation of signalling pathways associated with the B cell receptor. Our data suggest that c-Myc/Max heterodimers are not essential for the initiation of certain biological processes in B lymphocytes. Rather, c-Myc/Max are necessary for fine-tuning the initial response in these cells after activation. Overall design: B cell mRNA profiles of 8-week old control (HET) Myc deficient (MycKO), Max deficient (MaxKO) and double deficient (DKO) mice were generated by deep sequencing, in duplicate, using a HiSeq2500 (Illumina.

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Pérez-Olivares M, Trento A, Rodriguez-Acebes S, González-Acosta D, Fernández-Antorán D, Román-García S, Martinez D, López-Briones T, Torroja C, Carrasco YR, Méndez J, Moreno de Alborán I