Related Experiment Video

Updated: May 15, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Mimicking p14ARF phosphorylation influences its ability to restrain cell proliferation

Maria Vivo1, Michela Ranieri, Federica Sansone

  • 1Department of Structural and Functional Biology, University of Naples Federico II, Naples, Italy. maria.vivo@unina.it

Plos One
|January 12, 2013
PubMed

Insights

p14ARF, a tumor suppressor, is phosphorylated by PKC, affecting its stability and localization. This phosphorylation may help cancer cells evade growth arrest and apoptosis, promoting tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • The INK4a/ARF locus is frequently altered in human cancers.
  • ARF acts as a tumor suppressor by inducing cell cycle arrest or apoptosis.
  • ARF's role in oncogenic checkpoint pathways is well-established, but mechanisms of its turnover are less understood.

Purpose of the Study:

  • To investigate novel mechanisms regulating ARF turnover.
  • To identify post-translational modifications of p14ARF.
  • To explore the functional consequences of p14ARF phosphorylation.

Main Methods:

  • Bioinformatic prediction of protein kinase C (PKC) phosphorylation sites.
  • Site-directed mutagenesis of p14ARF (T8A and phosphomimetic T8D).
  • Analysis of p14ARF stability, localization, MDM2 binding, p53 stabilization, and cell growth arrest.

Main Results:

  • p14ARF is identified as a direct target of PKC.
  • Threonine 8 (T8) is a conserved phosphorylation site influencing ARF stability and localization.
  • A phosphomimetic mutation at T8 impairs p14ARF-mediated growth arrest but not MDM2 binding or p53 stabilization.

Conclusions:

  • PKC-mediated phosphorylation of p14ARF is a novel mechanism regulating its function.
  • Phosphorylation of p14ARF may allow cancer cells to escape ARF-mediated surveillance.
  • Targeting ARF phosphorylation could be a strategy to enhance anti-cancer therapies.

More Related Videos

Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

Related Concept Videos

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.
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...
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...
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...
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...