# Regulation of Cell Cycle progression by the nuclear envelope

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2024 · $323,473

## Abstract

PROJECT SUMMARY/ABSTRACT
 Under physiological conditions, cells are subjected to mechanical tension that triggers multiple signaling
pathways and impacts numerous cellular processes, including cell cycle progression. It is well established that
a dysfunction of these tension-sensitive signaling pathways can cause unbalanced proliferation and pathological
tissue remodeling; however, the precise molecular pathways remain poorly defined. As cells experience tension,
the nucleus undergoes significant morphological changes due to its connection with the cytoskeleton that
transmits mechanical force to the nuclear envelope. We recently showed that nuclear flattening activates
transcription factors that stimulate G1/S transition, leading us to hypothesize that the nuclear membrane could
serve as a tension sensor whose activation is necessary for cell cycle progression. Building on these findings,
as well as on the work of others, we will test this hypothesis by applying a combination of biophysics, imaging,
and biochemical approaches to define the nuclear tension-sensitive pathways that control cell cycle progression.
In Aim #1, we will determine whether RhoA-mediated pathways increase actomyosin contractility and nuclear
envelope tension during G1 to stimulate G1/S transition. In Aim#2, we will extend our investigation to the
signaling triggered in response to an increase in nuclear tension and we will define how these signaling events
promote entry into S phase. In Aim#3, we will determine whether tension transmitted to the nucleus during
interphase stimulates mitosis progression. We anticipate that the successful completion of this project will
increase our understanding of the tension-sensitive mechanisms controlling cell cycle progression and will
identify new pharmacological targets to limit cell proliferation in pathological contexts associated with excessive
actomyosin tension.

## Key facts

- **NIH application ID:** 10825592
- **Project number:** 5R01GM147823-02
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Christophe Daniel Guilluy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $323,473
- **Award type:** 5
- **Project period:** 2023-04-10 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825592

## Citation

> US National Institutes of Health, RePORTER application 10825592, Regulation of Cell Cycle progression by the nuclear envelope (5R01GM147823-02). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10825592. Licensed CC0.

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