STAT3 and PKC differentially regulate telomerase activity during megakaryocytic differentiation of K562 cells.
Telomerase is active in immature somatic cells, but not in differentiated cells. However, the regulation during cell differentiation is not well understood. In this study, a human chronic myelogenous leukemia cell line (K562) was induced to differentiate into megakaryocytes by TPA, and erythroid by STI571. A human acute myeloblastic leukemia cell line (HL60) was also induced to differentiate into monocytes by TPA and VD3, and granulocyte by ATRA. TPA induced transient increase of telomerase activity (mainly nuclear fraction) during megakaryocytic differentiation, while the expression of hTERT decreased gradually throughout the same period. Pretreatment with PKC inhibitors inhibited the megakaryocytic differentiation, transient increase of telomerase activity, while recombinant PKC increased telomerase activity. ChIP assay resulted STAT3 and STAT5 dissociated from the hTERT promoter, indicating that STAT3 and STAT5 are one of the transcriptional regulators. These results suggest that telomerase activity is regulated by two mechanisms during megakaryocytic differentiation.
Nakatake
Mayuka
M
Humanities and Sciences School, Ochanomizu University, Tokyo, Japan.
Kakiuchi
Yasutaka
Y
Sasaki
Narie
N
Murakami-Murofushi
Kimiko
K
Yamada
Osamu
O
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004121:Dimethyl Sulfoxide; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D000098:Acetophenones; D001578:Benzopyrans; D017931:DNA Primers; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C085746:rottlerin; D011493:Protein Kinase C; D019098:Telomerase; D004121:Dimethyl Sulfoxide