Prolyl isomerase Pin1 binds to and stabilizes acetyl CoA carboxylase 1 protein, thereby supporting cancer cell proliferation

Koji Ueda, Yusuke Nakatsu, Takeshi Yamamotoya, Hiraku Ono, Yuki Inoue, Masa Ki Inoue, Yu Mizuno, Yasuka Matsunaga, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Shin Ichiro Takahashi, Akio Matsubara, Tomoichiro Asano

研究成果: ジャーナルへの寄稿記事査読

21 被引用数 (Scopus)

抄録

The prolyl isomerase Pin1 expression level is reportedly increased in most malignant tissues and correlates with poor outcomes. On the other hand, acetyl CoA carboxylase 1 (ACC1), the rate limiting enzyme of lipogenesis is also abundantly expressed in cancer cells, to satisfy the demand for the fatty acids (FAs) needed for rapid cell proliferation. We found Pin1 expression levels to correlate positively with ACC1 levels in human prostate cancers, and we focused on the relationship between Pin1 and ACC1. Notably, it was demonstrated that Pin1 associates with ACC1 but not with acetyl CoA carboxylase 2 (ACC2) in the overexpression system as well as endogenously in the prostate cancer cell line DU145. This association is mediated by the WW domain in the Pin1 and C-terminal domains of ACC1. Interestingly, Pin1 deficiency or treatment with Pin1 siRNA or the inhibitor juglone markedly reduced ACC1 protein expression without affecting its mRNA level, while Pin1 overexpression increased the ACC1 protein level. In addition, chloroquine treatment restored the levels of ACC1 protein reduced by Pin1 siRNA treatment, indicating that Pin1 suppressed ACC1 degradation through the lysosomal pathway. In brief, we have concluded that Pin1 leads to the stabilization of and increases in ACC1. Therefore, it is likely that the growth-enhancing effect of Pin1 in cancer cells is mediated at least partially by the stabilization of ACC1 protein, corresponding to the well-known potential of Pin1 inhibitors as anti-cancer drugs.

本文言語英語
ページ(範囲)1637-1648
ページ数12
ジャーナルOncotarget
10
17
DOI
出版ステータス出版済み - 1 2月 2019
外部発表はい

フィンガープリント

「Prolyl isomerase Pin1 binds to and stabilizes acetyl CoA carboxylase 1 protein, thereby supporting cancer cell proliferation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル