Cell Cycle Control by Optogenetically Regulated Cell Cycle Inhibitor Protein p21

Author:

Lataster Levin1,Huber Hanna Mereth1,Böttcher Christina1,Föller Stefanie2ORCID,Takors Ralf2ORCID,Radziwill Gerald13ORCID

Affiliation:

1. Faculty of Biology, Institute of Biology II, University of Freiburg, 79098 Freiburg, Germany

2. Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, Germany

3. Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79098 Freiburg, Germany

Abstract

The progression through the cell cycle phases is driven by cyclin-dependent kinases and cyclins as their regulatory subunits. As nuclear protein, the cell cycle inhibitor p21/CDKN1A arrests the cell cycle at the growth phase G1 by inhibiting the activity of cyclin-dependent kinases. The G1 phase correlates with increased cell size and cellular productivity. Here, we applied an optogenetic approach to control the subcellular localization of p21 and its nuclear functions. To generate light-controllable p21, appropriate fusions with the blue light switch cryptochrome 2/CIBN and the AsLOV-based light-inducible nuclear localization signal, LINuS, were used. Both systems, p21-CRY2/CIB1 and p21-LINuS, increased the amounts of cells arrested in the G1 phase correlating with the increased cell-specific productivity of the reporter-protein-secreted alkaline phosphatase. Varying the intervals of blue LED light exposure and the light dose enable the fine-tuning of the systems. Light-controllable p21 implemented in producer cell lines could be applied to steer the uncoupling of cell proliferation and cell cycle arrest at the G1 phase optimizing the production of biotherapeutic proteins.

Funder

German Research Foundation

Germany’s Excellence Strategy

Publisher

MDPI AG

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology

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