Submitted November 29, 2006
Accepted August 12, 2007
The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKC
and ERK pathways
Gilles Despouy, Marjorie Joiner, Emilie Le Toriellec, Robert Weil, and Marc Henri Stern*
Centre de Recherche, Institut Curie, Paris, France
INSERM U830, Paris, France
CNRS URA 2582, Institut Pasteur, Paris, France
* Corresponding author; email: marc-henri.stern{at}curie.fr.
The TCL1/MTCP1 oncogenes were identified on the basis of their involvement in T-cell prolymphocytic leukemia (T-PLL). TCL1 and MTCP1 proteins directly interact with AKT and modulate the AKT signal-transduction pathway, but the relevance of this mechanism in leukemogenesis remains unclear. We investigate the biological functions of TCL1 in the T-cell lineage using various cell lines, and primary malignant and normal lymphocytes. In the Jurkat cell line, expression of TCL1 had no effect in unstimulated cells, whereas it abrogated activation-induced cell death (AICD). These cellular effects were concomitant with a major inhibition by TCL1 of PKC
and ERK pathways. Secondly, the TCL1-driven T-cell leukemia cell line SUP-T11 was shown to have impaired PKC and ERK phosphorylation upon stimulation, which were restored by TCL1 inhibition using RNA interference. Finally, defects in these pathways were also observed in primary malignant (T-PLL) and transduced normal T lymphocytes expressing TCL1. Altogether, our data demonstrated that TCL1 inhibits AICD in T-cells by blocking PKC and ERK activation, upon cellular activation.
