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  • 标题:The Truncated Isoform of the Receptor Tyrosine Kinase ALK Generated by Alternative Transcription Initiation (ALKATI) Induces Chromatin Structural Changes in the Nucleus in a Kinase Activity-Dependent Manner
  • 本地全文:下载
  • 作者:Yuki Takakura ; Noritaka Yamaguchi ; Takuya Honda
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2017
  • 卷号:40
  • 期号:11
  • 页码:1968-1975
  • DOI:10.1248/bpb.b17-00548
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Anaplastic lymphoma kinase (ALK) is a receptor-type tyrosine kinase that promotes cell growth upon stimulation with ligands such as midkine and pleiotrophin. Recently, a truncated isoform of ALK was identified in a variety of tumors. This isoform is expressed from a novel ALK transcript initiated from a de novo alternative transcription initiation (ATI) site in ALK intron 19 (referred to as ALKATI). ALKATI, which consists of only the intracellular kinase domain, localizes to the nucleus as well as the cytoplasm. However, its nuclear role is unknown. In this study, we determined that ALKATI promoted chromatin structural changes in the nucleus in a kinase activity-dependent manner. We found that expression of ALKATI increased the level of the heterochromatin marker Lys9 tri-methylated histone H3. In addition, we demonstrated that ALKATI phosphorylated the nuclear protein A-kinase anchoring protein 8 (AKAP8) and altered its subcellular localization from the insoluble fraction to the soluble fraction. These results suggest that ALKATI induces chromatin structural changes and heterochromatinization through phosphorylation of AKAP8 in the nucleus.

  • 关键词:anaplastic lymphoma kinase;nuclear tyrosine kinase;A-kinase anchoring protein 8;heterochromatinization;alternative transcription initiation;chromatin structural change
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