The Roles of RUNX Family Proteins in Development of Immune Cells

Abstract

The Runt-related transcription factors (RUNX) transcription factors have been known for their critical roles in numerous developmental processes and diseases such as autoimmune disorders and cancer. Especially, RUNX proteins are best known for their roles in hematopoiesis, particularly during the development of T cells. As scientists discover more types of new immune cells, the functional diversity of RUNX proteins also has been increased over time. Furthermore, recent research has revealed complicated transcriptional networks involving RUNX proteins by the current technical advances. Databases established by next generation sequencing data analysis has identified ever increasing numbers of potential targets for RUNX proteins and other transcription factors. Here, we summarize diverse functions of RUNX proteins mainly on lymphoid lineage cells by incorporating recent discoveries.

Keywords: Runx family; development; immune cells; transcription factors.

Fig. 1. Protein structure of RUNX family proteins.

All RUNX proteins have evolutionarily conserved Runx domains with DNA binding capability. Transactivation domain is required for the transcriptional activity of RUNX proteins by interacting with multiple proteins such as P300 and SMADS. The C-terminal penta-peptide sequences, VWRPY, is responsible for the recruitment of transcriptional co-repressors such as Groucho-TLE and HDACs. In addition, RUNX proteins are reported to be post-translationally modified by phosphorylation, acetylation, methylation and sumoylation.

Fig. 2. The function of RUNX proteins during T cell development.

Thymic T cell progenitors which are CD4^–CD8^– doublenegative (DN) progress in 4 stages (DN1 to 4) until becoming CD4⁺CD8⁺ double-positive (DP) expressing TCR on the cell surface. TCR expression requires TCR beta chain rearrangement which requires activation of a transcriptional enhancer, known as Eb, within the Tcrb gene by RUNX1. RUNX1 is also essential for the proliferation of DN4 cell during transition to the DP stage. RUNX proteins also play important roles in other lineages of T cells such as Treg, NKT, Th1, Th17, cytotoxic T cells, etc.