Highlighted Paper selected by Editor-in-Chief : The Truncated Isoform of the Receptor Tyrosine Kinase ALK Generated by Alternative Transcription Initiation (ALK[ATI]) Induces Chromatin Structural Changes in the Nucleus in a Kinase Activity-Dependent Manner

• Takakura Yuki

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

• Yamaguchi Noritaka

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

• Honda Takuya

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

• Morii Mariko

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

• Yuki Ryuzaburo

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

• Nakayama Yuji

  Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University

• Yamaguchi Naoto

  Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University

書誌事項

タイトル別名

• The Truncated Isoform of the Receptor Tyrosine Kinase ALK Generated by Alternative Transcription Initiation (ALK^ATI) Induces Chromatin Structural Changes in the Nucleus in a Kinase Activity-Dependent Manner
• The truncated isoform of the receptor tyrosine kinase ALK generated by alternative transcription initiation (ATLATI) induces chromatin structural changes in the nucleus in a kinase activity-dependent manner

抄録

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 ALK^ATI). ALK^ATI, 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 ALK^ATI promoted chromatin structural changes in the nucleus in a kinase activity-dependent manner. We found that expression of ALK^ATI increased the level of the heterochromatin marker Lys9 tri-methylated histone H3. In addition, we demonstrated that ALK^ATI 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 ALK^ATI induces chromatin structural changes and heterochromatinization through phosphorylation of AKAP8 in the nucleus.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 40 (11), 1968-1975, 2017

  公益社団法人 日本薬学会

キーワード

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

詳細情報

• CRID: 1390282679611155200
• NII論文ID: 130006191980
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b17-00548
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 028602370
• PubMed: 29093346
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028602370
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/11/40_b17-00548/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2018228602
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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