Related Experiment Video

Updated: May 22, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

p57(KIP2) control of actin cytoskeleton dynamics is responsible for its mitochondrial pro-apoptotic effect

E Kavanagh1, P Vlachos, V Emourgeon

  • 1Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

Cell Death & Disease
|May 18, 2012
PubMed

Insights

The tumor suppressor p57 (cyclin-dependent kinase inhibitor 1C) promotes cell death by stabilizing the actin cytoskeleton. This stabilization is crucial for p57

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • p57 (cyclin-dependent kinase inhibitor 1C) is a tumor suppressor often downregulated in cancer.
  • p57 regulates processes beyond cell cycle control, including apoptosis and cell migration.
  • p57 inhibits cell migration by stabilizing the actin cytoskeleton via LIM domain kinase-1 (LIMK-1).

Purpose of the Study:

  • To investigate the link between p57's pro-apoptotic effect and its influence on the actin cytoskeleton.
  • To elucidate the mechanism by which p57 promotes mitochondrial-mediated apoptosis.

Main Methods:

  • Utilized actin cytoskeleton-stabilizing (Jasplakinolide) and destabilizing (cytochalsin D) agents.
  • Assessed the requirement of LIMK-1 for p57's pro-apoptotic function.
  • Examined the association between p57-mediated actin stabilization and hexokinase-1 localization at mitochondria.

Main Results:

  • Actin cytoskeleton stabilization mimicked p57's pro-apoptotic effect, while destabilization reversed it.
  • LIMK-1 was essential for p57 to promote cell death.
  • p57-mediated actin stabilization led to hexokinase-1 displacement from mitochondria, facilitating apoptosis.

Conclusions:

  • p57's tumor suppressor function in promoting cell death is dependent on its ability to stabilize the actin cytoskeleton.
  • This study links p57's effects on the actin cytoskeleton to its role in initiating mitochondrial apoptosis.
  • The findings provide a mechanistic link between p57's cytoskeletal regulation and its tumor suppressor activity.

More Related Videos

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Aip1p Dynamics Are Altered by the R256H Mutation in Actin08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.