Calcineurin regulates cyclin D1 stability through dephosphorylation at T286

Takahiro Goshima, Makoto Habara, Keisuke Maeda, Shunsuke Hanaki, Yoichi Kato, Midori Shimada

Research output: Contribution to journalArticlepeer-review

Abstract

The Calcineurin/NFAT (nuclear factor of activated T cells) pathway plays an essential role in the tumorigenic and metastatic properties in breast cancer. The molecular mechanism of the antiproliferative effect of calcineurin inhibition, however, is poorly understood. We found that calcineurin inhibition delayed cell cycle progression at G1/S, and promoted cyclin D1 degradation by inhibiting dephosphorylation at T286. Importantly, overexpression of cyclin D1 partially rescued delayed G1/S progression, thereby revealing cyclin D1 as a key factor downstream of calcineurin inhibition. Cyclin D1 upregulation is observed in human invasive breast cancers, and our findings indicate that dysregulation of T286 phosphorylation could play a role in this phenomenon. We therefore propose that targeting site specific phosphorylation of cyclin D1 could be a potential strategy for clinical intervention of invasive breast cancer.

Original languageEnglish
Article number12779
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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