Related Experiment Video

Updated: May 22, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

The p57 CDKi integrates stress signals into cell-cycle progression to promote cell survival upon stress

Manel Joaquin1, Albert Gubern, Daniel González-Nuñez

  • 1Departament de Ciències Experimentals i de la Salut, Cell Signaling Research Group, Univeristat Pompeu Fabra, Barcelona, Spain. manel.joaquin@upf.edu

The EMBO Journal
|May 10, 2012
PubMed

Insights

The p38 stress-activated protein kinase (SAPK) targets p57(Kip2) to delay cell cycle progression. This phosphorylation enhances cell survival under various stresses by inhibiting cyclin-dependent kinase activity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The cyclin-dependent kinase inhibitor p57(Kip2) plays roles in development and senescence, but its function in cell cycle control under stress is unclear.
  • Stress-activated protein kinases (SAPKs) are crucial for cellular responses to environmental challenges.

Purpose of the Study:

  • To elucidate the role of p57(Kip2) in cell cycle regulation during stress.
  • To investigate the interaction between p38 SAPK and p57(Kip2) in response to cellular stress.

Main Methods:

  • Western blotting to detect protein phosphorylation.
  • Genetic manipulation (inactivation of SAPK or p57(Kip2)).
  • Cell viability assays under various stress conditions (osmotic, oxidative).

Main Results:

  • p38 SAPK phosphorylates p57(Kip2) at T143, enhancing its inhibition of Cdk2.
  • This phosphorylation leads to cell-cycle delay in response to osmotic stress.
  • Genetic inactivation of p38 or p57(Kip2) abrogates stress-induced cell-cycle delay and reduces cell viability.
  • p38-mediated p57(Kip2) phosphorylation is induced by oxidative stress and ionomycin, with cells lacking p38 or p57 showing reduced viability.

Conclusions:

  • Cell survival under diverse stresses relies on p38-mediated phosphorylation of p57(Kip2), which inhibits CDK activity.
  • This pathway represents a novel mechanism for delaying cell cycle progression to enhance cellular resilience to stress.

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...