Integrin α11 is enriched in quiescence and promotes cell-cycle re-entry through destabilisation of the CDK inhibitor p27
- 1MRC Laboratory of Medical Sciences
Abstract
Proteins that distinguish quiescent cells from other non-proliferative states and actively regulate their return to proliferation remain poorly understood. Here, we combined quantitative proteomics with functional image-based screening to identify regulators of the quiescence-to-proliferation transition. Amongst the functional quiescence signature proteins we identified, we focussed on integrin 11 (ITGA11) which is induced across multiple models of reversible quiescence in distinct cell types and that has low expression in proliferating and senescent cells. Although ITGA11 is dispensable for proliferation of asynchronously cycling cells, it is required for efficient cell-cycle re-entry from quiescence. Mechanistically, ITGA11 promotes YAP accumulation and nuclear localization, thereby sustaining SKP2 expression and p27 degradation during cell cycle re-entry. Depletion of p27, or pharmacological activation of YAP signalling rescues the cell-cycle re-entry defect caused by ITGA11 depletion. Together, these findings identify ITGA11 as a functional quiescence signature protein that couples extracellular matrix sensing to YAP-dependent regulation of the Skp2-p27 axis, revealing a mechanism that controls the transition from quiescence to proliferation.
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BibTeX
@misc{kaur2026integrin,
title = {{Integrin α11 is enriched in quiescence and promotes cell-cycle re-entry through destabilisation of the CDK inhibitor p27}},
author = {E. Kaur and J. A. Holt and R. Wilson and V. Kelly and E. G. Marin and B. Zunar and A. Daniels and R. Adib and P. Thomas and B. Lenhard and T. Ly and A. R. Barr},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.748043},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.748043v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Integrin α11 is enriched in quiescence and promotes cell-cycle re-entry through destabilisation of the CDK inhibitor p27
AU - E. Kaur
AU - J. A. Holt
AU - R. Wilson
AU - V. Kelly
AU - E. G. Marin
AU - B. Zunar
AU - A. Daniels
AU - R. Adib
AU - P. Thomas
AU - B. Lenhard
AU - T. Ly
AU - A. R. Barr
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.748043
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.748043v1
AB - Proteins that distinguish quiescent cells from other non-proliferative states and actively regulate their return to proliferation remain poorly understood. Here, we combined quantitative proteomics with functional image-based screening to identify regulators of the quiescence-to-proliferation transition. Amongst the functional quiescence signature proteins we identified, we focussed on integrin 11 (ITGA11) which is induced across multiple models of reversible quiescence in distinct cell types and that has low expression in proliferating and senescent cells. Although ITGA11 is dispensable for proliferation of asynchronously cycling cells, it is required for efficient cell-cycle re-entry from quiescence. Mechanistically, ITGA11 promotes YAP accumulation and nuclear localization, thereby sustaining SKP2 expression and p27 degradation during cell cycle re-entry. Depletion of p27, or pharmacological activation of YAP signalling rescues the cell-cycle re-entry defect caused by ITGA11 depletion. Together, these findings identify ITGA11 as a functional quiescence signature protein that couples extracellular matrix sensing to YAP-dependent regulation of the Skp2-p27 axis, revealing a mechanism that controls the transition from quiescence to proliferation.
ER -