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Multistep regulation of telomerase during differentiation of HL60 cells
Author(s) -
Yamada Osamu,
Ozaki Kohji,
Nakatake Mayuka,
Akiyama Masaharu,
Kawauchi Kiyotaka,
Matsuoka Rumiko
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1207848
Subject(s) - telomerase , biology , cellular differentiation , protein kinase b , microbiology and biotechnology , telomerase reverse transcriptase , ly294002 , differentiation therapy , pi3k/akt/mtor pathway , telomere , retinoic acid , cancer research , cell culture , signal transduction , acute promyelocytic leukemia , biochemistry , gene , genetics
Using three different differentiation agents (1α, 25 dihydroxyvitamin D3, all‐ trans ‐retinoic acid, and Am80), down‐regulation of telomerase activity was found to be a common response during the monocytic or granulocytic differentiation of human acute myeloblastic leukemia cell line 60 (HL60) cells. Rapid down‐regulation of telomerase transcription occurred during early differentiation of HL60 cells prior to G 1 arrest. Akt kinase activity was suppressed after 6 h of differentiation along with inhibition of telomerase activity, and the extent of the suppression that occurred while maintaining telomerase protein expression suggested the post‐translational regulation of telomerase activity. Recombinant Akt dose‐dependently increased telomerase activity, and telomerase was inhibited at the transcriptional and post‐translational levels by LY294002, suggesting that PI‐3K/Akt is one of the key signaling proteins involved in telomerase regulation. Each of the three differentiation agents caused a significant increase of signaling proteins (including Akt) at 3 days after the initiation of differentiation. Changes of acetyl‐histone H4, which regulates transcription of the telomerase gene, were observed before the activation of Akt. This finding suggests that epigenetic control of telomerase transcription occurs before activation of Akt during the late stage of differentiation. These results indicate that telomerase activity is regulated by at least two mechanisms during granulocytic and monocytic differentiation, with one mechanism being transcriptional and the other being post‐translational.