Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells

Norihisa Uehara, Katsuhiko Yoshizawa, Airo Tsubura

研究成果: ジャーナルへの寄稿学術誌査読

18 被引用数 (Scopus)

抄録

Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCF Skp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostatinduced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostatinduced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

本文言語英語
ページ(範囲)105-110
ページ数6
ジャーナルOncology reports
28
1
DOI
出版ステータス出版済み - 7月 2012
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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