Human telomerase is regulated by erythropoietin and transforming growth factor-beta in human erythroid progenitor cells.
Telomerase catalytic subunit (hTERT) exerts important cellular functions including telomere homeostasis, genetic stability, cell survival and perhaps differentiation. However, the nature of external or internal signals, which regulate hTERT expression in tissues, remains poorly understood. Thus, whereas it has been described that hTERT gene is regulated along the differentiation of primitive myeloid progenitors, the effect of specific cytokines on telomerase expression in each myeloid lineage is currently unknown. Based on these considerations, we have investigated hTERT expression in erythroid cells treated with erythropoietin (EPO) and transforming growth factor beta (TGFbeta), as putative positive and negative regulators, respectively. We describe here that EPO activates hTERT gene transcription in in vitro-expanded primary erythroid precursors as well as in UT7 erythroleukemia cells. In UT7 cells, this study shows also that EPO acts through a JAK2/STAT5/c-myc axis. In contrast, TGFbeta blocks EPO signaling downstream of c-myc induction through a Smad3-dependent mechanism. Finally, hTERT appears to be efficiently regulated by EPO and TGFbeta in an opposite way in erythropoietic cells, arguing for a role of telomerase in red blood cell production.
Prade-Houdellier
N
N
INSERM U563, Toulouse, France.
Frébet
E
E
Demur
C
C
Gautier
E-F
EF
Delhommeau
F
F
Bennaceur-Griscelli
A-L
AL
Gaudin
C
C
Martinel
V
V
Laurent
G
G
Mansat-De Mas
V
V
Beyne-Rauzy
O
O
D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D018952:Antigens, CD34; D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta; D004921:Erythropoietin; D019098:Telomerase