A minimal fate-selection switch. (December 2015)

• Record Type: Journal Article
• Authors: Weinberger, Leor S
• Is Part Of: Current opinion in cell biology. Volume 37(2015)
• Page Start: 111
• Page End: 118
• Publication Date: 2015-12
• Subjects: Cells -- Periodicals; Cytology -- Periodicals; Cell Biology -- Periodicals; Biology -- Periodicals; Cells -- Periodicals; Review Literature -- Periodicals; Cell Biology; Biology; Cells; Review Literature; Cellules -- Périodiques; Cytologie -- Périodiques; Electronic journals; 571.6
• DOI: 10.1016/j.ceb.2015.10.005
• Languages: English
• ISSNs: 0955-0674

Abstract

Abstract : 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.