RT Journal Article
SR Electronic
T1 Chemically Tunable FOXM1-D Sensor Revealed FOXM1 Direct Influence on Cell Cycle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.03.01.530713
DO 10.1101/2023.03.01.530713
A1 Kriengkrai Phongkitkarun
A1 Porncheera Chusorn
A1 Maliwan Kamkaew
A1 Eric W.-F. Lam
A1 Chamras Promptmas
A1 Somponnat Sampattavanich
YR 2023
UL http://biorxiv.org/content/early/2023/03/02/2023.03.01.530713.abstract
AB Forkhead box protein M1 (FOXM1) is a proliferation-associated transcription factor contributing to the G2/M phase transition of the cell cycle. Although the upregulation of FOXM1 has been observed in different cancer types, how the regulation of FOXM1 dynamically alters during cell cycles and potentially contributes to tumorigenesis is not well understood. We showed here the development and application of a tunable FOXM1-DHFR (FOXM1-D) sensor that enables surveillance and manipulation of the FOXM1 abundance. Using trimethoprim (TMP) to stabilize the sensor, we measured the kinetics of FOXM1-D production, degradation, and cytosolic-to-nuclear translocation in the G1 and G2 cell-cycle phases. By controlling FOXM1-D stability in different synchronized cell cycle pools, we found that the G1- and S-synchronized cells finished their first cell division faster, although the G2-synchronized cells were unaffected. Our analysis of single-cell FOXM1-D dynamics revealed that the two-round dividing cells had a lower amplitude and later peak time than those arrested in the first cell division. Destabilizing FOXM1-D in the single-round dividing cells enabled these cells to re-enter the second cell division, proving that overproduction of FOXM1 causes cell cycle arrest and prevents unscheduled proliferation.Competing Interest StatementThe authors have declared no competing interest.