Cell cycle control by optogenetically regulated cell cycle inhibitor protein p21

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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Biology. - 12, 9 (2023) , 1194, ISSN: 2079-7737

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2023
Creator
Lataster, Levin
Huber, Hanna Mereth
Böttcher, Christina
Föller, Stefanie
Takors, Ralf
Radziwill, Gerald

DOI
10.3390/biology12091194
URN
urn:nbn:de:bsz:25-freidok-2390619
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:57 AM CEST

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Associated

Time of origin

  • 2023

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