Nakatake Mayuka, Kakiuchi Yasutaka, Sasaki Narie, Murakami-Murofushi Kimiko, Yamada Osamu
Humanities and Sciences School, Ochanomizu University, Tokyo, Japan.
Cell Cycle. 2007 Jun 15;6(12):1496-501. Epub 2007 Apr 18.
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.
端粒酶在未成熟体细胞中具有活性，但在分化细胞中则无活性。然而，细胞分化过程中的调控机制尚未完全明确。在本研究中，人慢性髓性白血病细胞系（K562）经佛波酯（TPA）诱导分化为巨核细胞，经甲磺酸伊马替尼（STI571）诱导分化为红细胞。人急性髓性白血病细胞系（HL60）也经TPA和维生素D3（VD3）诱导分化为单核细胞，经全反式维甲酸（ATRA）诱导分化为粒细胞。在巨核细胞分化过程中，TPA诱导端粒酶活性（主要是核部分）短暂增加，而在同一时期，人端粒酶逆转录酶（hTERT）的表达逐渐下降。蛋白激酶C（PKC）抑制剂预处理可抑制巨核细胞分化以及端粒酶活性的短暂增加，而重组PKC则可增加端粒酶活性。染色质免疫沉淀（ChIP）分析结果显示，信号转导和转录激活因子3（STAT3）和信号转导和转录激活因子5（STAT5）与hTERT启动子解离，表明STAT3和STAT5是转录调节因子之一。这些结果提示，在巨核细胞分化过程中端粒酶活性受两种机制调控。
