A Role for Bcl-2 in Notch1-Dependent Transcription in Thymic Lymphoma Cells

Abstract EN

Notch1 is a transcription factor important for T-cell development.

Notch1 is active in double negative (DN) thymocytes, while being depressed in double positive (DP) thymocytes.

Synchronously, the expression of Bcl-2 becomes downregulated during the transition from DN to DP thymocytes.

We previously observed that overexpression of an intracellular active Notch1 (ICN) in Bcl-2-positive 2B4 T cells leads to the transcription of Notch1-regulated genes.

However, these genes were not induced in Bcl-2-negative DP PD1.6 thymic lymphoma cells overexpressing ICN.

Here we show that, when Bcl-2 is simultaneously introduced into these cells, Notch-regulated genes are transcribed.

Only in the presence of both Bcl-2 and ICN, PD1.6 thymic lymphoma cells become resistant to glucocorticoid (GC)-induced apoptosis.

Our data suggest that Bcl-2 plays a role in modulating Notch1 function in T cells.