論文

査読有り
2019年9月1日

DMPK is a New Candidate Mediator of Tumor Suppressor p53-Dependent Cell Death

Molecules
  • Katsuhiko Itoh
  • ,
  • Takahiro Ebata
  • ,
  • Hiroaki Hirata
  • ,
  • Takeru Torii
  • ,
  • Wataru Sugimoto
  • ,
  • Keigo Onodera
  • ,
  • Wataru Nakajima
  • ,
  • Ikuno Uehara
  • ,
  • Daisuke Okuzaki
  • ,
  • Shota Yamauchi
  • ,
  • Yemima Budirahardja
  • ,
  • Takahito Nishikata
  • ,
  • Nobuyuki Tanaka
  • ,
  • Keiko Kawauchi

24
17
開始ページ
3175
終了ページ
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/molecules24173175
出版者・発行元
MDPI AG

Tumor suppressor p53 plays an integral role in DNA-damage induced apoptosis, a biological process that protects against tumor progression. Cell shape dramatically changes when cells undergo apoptosis, which is associated with actomyosin contraction; however, it remains entirely elusive how p53 regulates actomyosin contraction in response to DNA-damaging agents. To identify a novel p53 regulating gene encoding the modulator of myosin, we conducted DNA microarray analysis. We found that, in response to DNA-damaging agent doxorubicin, expression of myotonic dystrophy protein kinase (DMPK), which is known to upregulate actomyosin contraction, was increased in a p53-dependent manner. The promoter region of DMPK gene contained potential p53-binding sequences and its promoter activity was increased by overexpression of the p53 family protein p73, but, unexpectedly, not of p53. Furthermore, we found that doxorubicin treatment induced p73 expression, which was significantly attenuated by downregulation of p53. These data suggest that p53 induces expression of DMPK through upregulating p73 expression. Overexpression of DMPK promotes contraction of the actomyosin cortex, which leads to formation of membrane blebs, loss of cell adhesion, and concomitant caspase activation. Taken together, our results suggest the existence of p53-p73-DMPK axis which mediates DNA-damage induced actomyosin contraction at the cortex and concomitant cell death.

リンク情報
DOI
https://doi.org/10.3390/molecules24173175
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31480541
URL
https://www.mdpi.com/1420-3049/24/17/3175/pdf
ID情報
  • DOI : 10.3390/molecules24173175
  • eISSN : 1420-3049
  • ORCIDのPut Code : 62596907
  • PubMed ID : 31480541

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