PML-RARα and its phosphorylation regulate PML oligomerization and HIPK2 stability

Yutaka Shima, Yuki Honma, Issay Kitabayashi

研究成果: ジャーナルへの寄稿学術論文査読

14 被引用数 (Scopus)

抄録

The PML gene is frequently fused to the retinoic acid receptor a (RARa) gene in acute promyelocytic leukemia (APL), generating a characteristic PML-RARa oncogenic chimera. PML-RARα disrupts the discrete nuclear speckles termed nuclear bodies, which are formed in PML, suggesting that nuclear body disruption is involved in leukemogenesis. Nuclear body formation that relies upon PML oligomerization and its stabilization of the hypoxia-inducible protein kinase (HIPK)-2 is disrupted by expression of the PML-RARα chimera. Here, we report that disruption of nuclear bodies is also mediated by PML-RARα inhibition of PML oligomerization. PKA-mediated phosphorylation of PML-RARα blocked its ability to inhibit PML oligomerization and destabilize HIPK2. Our results establish that both PML oligomerization and HIPK2 stabilization at nuclear bodies are important for APL cell differentiation, offering insights into the basis for the most common prodifferentiation therapies of APL used clinically.

本文言語英語
ページ(範囲)4278-4288
ページ数11
ジャーナルCancer Research
73
14
DOI
出版ステータス出版済み - 15-07-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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