Kogulan Yoganathan

Abstract Proliferation is tightly regulated during T cell development, and is limited to immature CD4−CD8− thymocytes. The major proliferative event is initiated at the ‘β-selection’ stage following successful rearrangement of Tcrβ, and is triggered by and dependent on concurrent signaling by Notch and the pre-T cell receptor (TCR); however, it is unclear how these signals cooperate to promote cell proliferation.

The rearrangement of protein domains is known to have key roles in the evolution of signaling networks and, consequently, is a major tool used to synthetically rewire networks. However, natural mutational events leading to the creation of proteins with novel domain combinations, such as in frame fusions followed by domain loss, retrotranspositions, or translocations, to name a few, often simultaneously replace pre-existing genes.