Wnt-1 signal induces, phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK

Chie Kanei-Ishii, Jun Ninomiya-Tsuji, Jun Tanikawa, Teruaki Nomura, Tohru Ishitani, Satoshi Kishida, Kenji Kokura, Toshihiro Kurahashi, Emi Ichikawa-Iwata, Yongsok Kim, Kunihiro Matsumoto, Shunsuke Ishii

研究成果: Contribution to journalArticle査読

149 被引用数 (Scopus)

抄録

The c-myb proto-oncogene product (c-Myb) regulates both the proliferation and apoptosis of hematopoietic cells by inducing the transcription of a group of target genes. However, the biologically relevant molecular mechanisms that regulate c-Myb activity remain unclear. Here we report that c-Myb protein is phosphorylated and degraded by Wnt-1 signal via the pathway involving TAK1 (TGF-β-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase). Wnt-1 signal causes the nuclear entry of TAK1, which then activates HIPK2 and the mitogen-activated protein (MAP) kinase-like kinase NLK. NLK binds directly to c-Myb together with HIPK2, which results in the phosphorylation of c-Myb at multiple sites, followed by its ubiquitination and proteasome-dependent degradation. Furthermore, overexpression of NLK in M1 cells abrogates the ability of c-Myb to maintain the undifferentiated state of these cells. The down-regulation of Myb by Wnt-1 signal may play an important role in a variety of developmental steps.

本文言語英語
ページ(範囲)816-829
ページ数14
ジャーナルGenes and Development
18
7
DOI
出版ステータス出版済み - 4 1 2004

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 発生生物学

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