Procaspase activating compound 1 controls tetracycline repressor-regulated gene expression system

Author:

Song Chiman12,Kim Namkyoung3,Park Miri1,Lee Jiyeon1,Oh Ki-Bong2,Sim Taebo13ORCID

Affiliation:

1. Chemical Kinomics Research Center, Korea Institute of Science and Technology, 5 Hwarangro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea

2. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea

3. KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea

Abstract

Abstract The tetracycline repressor (TetR)-regulated system is a widely used tool to study gene functions through control of its expression. Various effectors such as tetracycline (Tc) and doxycycline (Dox) quickly induce or shut down gene expression, but reversing gene expression has not been eligible due to long half-lives of such effectors. Here, we found that procaspase activating compound 1 (PAC-1) rapidly reduces transient expression of TetR-regulated green fluorescent protein (GFP) in mammalian cells. Next, we applied PAC-1 to control of expression of transient receptor potential melastatin 7 (TRPM7) protein, whose downstream cellular events can be monitored by cell morphological changes. We observed that PAC-1 quickly reduces TRPM7 expression, consequently affecting cell morphology regulated by TRPM7. The present study demonstrates the first small molecule that efficiently turns off the TetR-regulated gene expression in mammalian cells, thereby precisely regulating the expression level of target gene.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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