Post-translational modifications of the E2A gene products and their roles in B lymphocyte development
- Author(s): Teachenor, Robert Thomas;
- et al.
E-proteins constitute a highly conserved family of helix- loop-helix proteins that modulate the developmental progression of a wide variety of developmental pathways. Prominent among the E-proteins are the E2A gene products, E12 and E47. E2A proteins play a critical role throughout B cell development, including specification, commitment and developmental progression. How the activity of E2A proteins is regulated has been a topic of intense investigation during the past two decades. However, previous studies have been mostly focused on a distinct class of helix-loop-helix proteins, named the Id proteins. Here we have examined another level of regulation involving the role of E47 phosphorylated serine residues in B-lineage development. Specifically, we have examined the role of phosphorylated residues in the E2A transactivation domains as well as a putative AKT substrate site in E47. Replacement of E2A phosphorylated serine residues in the E2A transactivation domains modestly but significantly affected B cell development. On the other hand, mutation of the E47 AKT substrate site in the mouse germ-line substrate site did not grossly affect B cell development neither in the bone marrow nor in the peripheral lymphoid organs. Finally, we found that whereas depletion of Id4 only modestly interfered with loss-of- PTEN mediated lymphomagenesis, forced E47 expression suppressed the development of lymphoma in PTEN-deficient mice. We propose a model in which the PI3K-AKT axis and E47 are linked but that AKT acts on multiple functionally redundant components of the E-protein machinery in order to modulate developmental progression and cell growth