A minimal fate-selection switch

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• 作者：Leor S Weinberger ^{leor.weinberger@ucsf.edu" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Current Opinion in Cell Biology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：37
• 期：Complete
• 页码：111-118
• 全文大小：1269 K

文摘

To preserve fitness in unpredictable, fluctuating environments, a range of biological systems probabilistically generate variant phenotypes — a process often referred to as ‘bet-hedging’, after the financial practice of diversifying assets to minimize risk in volatile markets. The molecular mechanisms enabling bet-hedging have remained elusive. Here, we review how HIV makes a bet-hedging decision between active replication and proviral latency, a long-lived dormant state that is the chief barrier to an HIV cure. The discovery of a virus-encoded bet-hedging circuit in HIV revealed an ancient evolutionary role for latency and identified core regulatory principles, such as feedback and stochastic ‘noise’, that enable cell-fate decisions. These core principles were later extended to fate selection in stem cells and cancer, exposed new therapeutic targets for HIV, and led to a potentially broad strategy of using ‘noise modulation’ to redirect cell fate.