The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKCtheta and ERK pathways.
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 biologic 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 PKCtheta and ERK pathways. Secondly, the TCL1-driven T-cell leukemia cell line SUP-T11 was shown to have impaired PKCtheta 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 PKCtheta and ERK activation, upon cellular activation.
Despouy
Gilles
G
Institut Curie, Centre de Recherche, Paris, France.
Joiner
Marjorie
M
Le Toriellec
Emilie
E
Weil
Robert
R
Stern
Marc Henri
MH
D016923:Cell Death; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation; D015513:Oncogene Proteins / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000074121:Protein Kinase C-theta; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; C082870:MTCP1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D048049:Extracellular Signal-Regulated MAP Kinases