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Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
Published on: February 16, 2015
Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration
Daniel R Croft1, Mathew L Coleman, Shuixing Li
1Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
The Journal of Cell Biology
|January 20, 2005
Summary
Apoptotic nuclear disintegration requires ROCK-mediated actin-myosin contraction and lamin proteolysis. This process is distinct from mitosis, relying on actin forces rather than microtubule dynamics.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis involves programmed cell death, characterized by distinct morphological and biochemical events.
- Membrane blebbing during apoptosis is linked to caspase activation and ROCK I activity.
- Nuclear integrity breakdown is a hallmark of late-stage apoptosis.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying nuclear disintegration during apoptosis.
- To determine the role of ROCK (Rho-associated protein kinase) and actin-myosin contractility in nuclear breakdown.
- To compare the mechanisms of nuclear disintegration in apoptosis versus mitosis.
Main Methods:
- Investigated the requirement of ROCK activity, myosin light chain (MLC) phosphorylation, and MLC ATPase activity for nuclear disruption.
- Assessed the role of the actin and microtubular cytoskeleton in maintaining nuclear integrity during apoptosis.
- Utilized conditional ROCK I activation in lamin A/C null and wild-type fibroblasts.
- Examined the effect of ROCK or MLC ATPase inhibition on caspase-mediated degradation of nuclear lamins.
Main Results:
- ROCK activity, MLC phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton are essential for apoptotic nuclear disintegration.
- The microtubular cytoskeleton is not required for nuclear breakdown during apoptosis.
- Inhibition of ROCK or MLC ATPase activity preserves nuclear integrity without affecting lamin degradation.
- Conditional ROCK I activation induced nuclear tearing in lamin A/C null fibroblasts but not in wild-type cells.
Conclusions:
- Apoptotic nuclear disintegration is driven by actin-myosin contractile forces and proteolysis of nuclear lamins.
- This mechanism is analogous to, yet distinct from, nuclear envelope breakdown during mitosis, which relies on microtubule forces and lamin phosphorylation/depolymerization.
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