Role of the leukemia-associated transcription factor STAT3 in platelet physiology.
Actinomycin D, a transcriptional inhibitor, was found to inhibit platelet potentiation by thrombopoietin (TPO), suggesting that TPO stimulation of platelets involves mitochondrial transcription. We sought to determine a possible role for leukemia-associated signal transducers and activators of transcription (STAT) proteins as mitochondrial transcription factors, focusing specifically on STAT3 in human platelets. We found TPO stimulation of platelets activated STAT3 in vitro, that STAT3 was present in platelet mitochondrial-rich fractions as determined by Western Blot analysis and was capable of binding to the regulatory D-loop region of human mitochondrial DNA upon activation. These results suggest that platelet signaling pathways activated by TPO may affect mitochondrial transcription via activation of STAT3.
Vassilev
Alexei O
AO
Department of Biochemistry, Parker Hughes Cancer Center, Parker Hughes Institute, St. Paul, MN 55113, USA.
Lorenz
David R
DR
Tibbles
Heather E
HE
Uckun
Fatih M
FM
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D004336:Drug Antagonism; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013926:Thrombopoietin / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D003609:Dactinomycin; D013926:Thrombopoietin