c-Myb Promotes the Survival of CD4+CD8+ Double-Positive Thymocytes through Upregulation of Bcl-xL

Abstract

Material Supplementary 6.DC1http://www.jimmunol.org/content/suppl/2010/02/09/jimmunol.090284

The Catalytic Activity of the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 3 Is Required To Sustain CD4+ CD8+ Thymocyte Survival

“…Reduced secondary TCR␣ gene rearrangement is observed in several experimental systems where DP thymocyte survival is compromised (26,(29)(30)(31)(32), since a certain time window is required for thymocytes to perform these successive TCR␣ gene rearrangements. Accordingly, ERK3-deficient DP thymocytes show an increased rate of apoptosis, which suggests that they have a shorter life span, explaining the reduced usage of distal TCR␣ locus rearrangement.…”

“…7C). This reduction in distal TCR␣ gene rearrangement has been observed in several mouse models where DP thymocyte survival is compromised (26,(29)(30)(31)(32), since DP thymocytes need to survive long enough to make successive rounds of secondary TCR␣ gene rearrangement. To test if ERK3 loss reduces DP thymocyte survival, we measured the expression of pro-and antiapoptotic molecules known to affect the survival of DP thymocytes.…”

“…Several transcription factors (c-Myb, ROR␥t, TCF-1, and HEB) are important for the proper expression of Bcl-x L in DP thymocytes (26,(29)(30)(31)(32). The ablation of their expression in genetically modified mouse models leads to impaired DP thymocyte survival and reduced TCR␣ secondary gene rearrangements (26,(29)(30)(31)(32).…”

Programmed Cell Death in T Cell Development

“…For example, pre-TCR signaling induces expression of the transcription factor T cell factor 1 (TCF-1), which associates with β-catenin to execute Wnt signaling (Goux et al 2005). TCF-1 -/-thymocytes have reduced expression of RORγt and Bcl-xL (Yuan et al 2010); only TCF-1 isoforms that can interact with β-catenin are able to induce Bcl-xL expression and rescue survival of TCF-1 -/-DP thymocytes (Ioannidis et al 2001). These data suggest that pre-TCR signaling and Wnt signaling cooperate to promote DP survival.…”

“…Activated AMPK enacts metabolic changes to promote cell survival, and in DP thymocytes, its mechanism appears to include RORγt and Bcl-xL expression (Cao et al 2010). Aside from TCF-1 and RORγt, the transcription factor c-myb is also thought to induce Bcl-xL expression in DP thymocytes in a TCF-1 and RORγt-independent manner (Yuan et al 2010). …”