Parental B-MYB/FOXM1 controls mitotic E2F to determine daughter cell fate
- 1Weill Cornell Medicine
Abstract
Mitogens trigger cell-cycle entry by activating E2F at the restriction point, which is followed by B-MYB/FOXM1 activation and progression to mitosis. How mitogens control continued cycling and cell-cycle exit after the restriction point is not well-understood. By developing an E2F and B-MYB/FOXM1 dual transcriptional biosensor system, we show that S/G2 phase duration is set by timed mitogen-regulated B-MYB/FOXM1 activation, while E2F activity gradually declines before mitosis. As a striking consequence, rapid B-MYB/FOXM1 activation shortens S/G2, delivering high mitotic E2F activity to daughter cells which keeps them cycling. Delayed B-MYB/FOXM1 activation prolongs S/G2, depleting mitotic E2F which drives daughters to quiescence. When S/G2 is further prolonged, partially activated B-MYB/FOXM1 frequently reverts, triggering mitotic bypass and polyploid quiescence. Thus, B-MYB/FOXM1 governs a tri-directional (G2 restriction point) where cells commit to continued cycling through early B-MYB/FOXM1 activation; cell-cycle exit through delayed B-MYB/FOXM1 activation; or mitotic bypass by B-MYB/FOXM1 inactivation.
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BibTeX
@misc{meyer2026parental,
title = {{Parental B-MYB/FOXM1 controls mitotic E2F to determine daughter cell fate}},
author = {T. MEYER and D. Rosenthal and T. Tsuruoka and V. Govindaraj and Y. Konagaya and B. Gong and S. Upadhya and N. Ratnayeke and D. Saha and W. Xia and M. Teruel},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753170},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753170v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Parental B-MYB/FOXM1 controls mitotic E2F to determine daughter cell fate
AU - T. MEYER
AU - D. Rosenthal
AU - T. Tsuruoka
AU - V. Govindaraj
AU - Y. Konagaya
AU - B. Gong
AU - S. Upadhya
AU - N. Ratnayeke
AU - D. Saha
AU - W. Xia
AU - M. Teruel
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753170
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753170v1
AB - Mitogens trigger cell-cycle entry by activating E2F at the restriction point, which is followed by B-MYB/FOXM1 activation and progression to mitosis. How mitogens control continued cycling and cell-cycle exit after the restriction point is not well-understood. By developing an E2F and B-MYB/FOXM1 dual transcriptional biosensor system, we show that S/G2 phase duration is set by timed mitogen-regulated B-MYB/FOXM1 activation, while E2F activity gradually declines before mitosis. As a striking consequence, rapid B-MYB/FOXM1 activation shortens S/G2, delivering high mitotic E2F activity to daughter cells which keeps them cycling. Delayed B-MYB/FOXM1 activation prolongs S/G2, depleting mitotic E2F which drives daughters to quiescence. When S/G2 is further prolonged, partially activated B-MYB/FOXM1 frequently reverts, triggering mitotic bypass and polyploid quiescence. Thus, B-MYB/FOXM1 governs a tri-directional (G2 restriction point) where cells commit to continued cycling through early B-MYB/FOXM1 activation; cell-cycle exit through delayed B-MYB/FOXM1 activation; or mitotic bypass by B-MYB/FOXM1 inactivation.
ER -