SR9009 Has REV-ERB-independent Effects on Cell Proliferation and Metabolism

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 May 26

PMID 31127047

Citations 82

Authors

Pieterjan Dierickx

Matthew J Emmett

Chunjie Jiang

Kahealani Uehara

Manlu Liu

Marine Adlanmerini

Mitchell A Lazar

Affiliations

Soon will be listed here.

Abstract

The nuclear receptors REV-ERBα and -β link circadian rhythms and metabolism. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well as diseased animal models and cell systems. However, the direct involvement of REV-ERBs in these effects of SR9009 has not been thoroughly assessed, as experiments were not performed in the complete absence of both proteins. Here, we report the generation of a mouse model for conditional genetic deletion of REV-ERBα and -β. We show that SR9009 can decrease cell viability, rewire cellular metabolism, and alter gene transcription in hepatocytes and embryonic stem cells lacking both REV-ERBα and -β. Thus, the effects of SR9009 cannot be used solely as surrogate for REV-ERB activity.

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