Related Experiment Video

Updated: Aug 9, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Subcellular targeting of p33ING1b by phosphorylation-dependent 14-3-3 binding regulates p21WAF1 expression

Wei Gong1, Michael Russell, Keiko Suzuki

  • 1Southern Alberta Cancer Research Institute, Dept. of Biochemistry, University of Calgary, #370 Heritage Medical Research Building, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.

Molecular and Cellular Biology
|April 4, 2006
PubMed

Insights

The tumor suppressor ING1 interacts with 14-3-3 proteins, which can tether ING1 in the cytoplasm. This mislocalization inhibits ING1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • ING1 (Inhibitor of Growth 1) functions as a type II tumor suppressor.
  • ING1 regulates crucial cellular processes including growth, stress signaling, apoptosis, and DNA repair.
  • Reduced ING1 expression and mislocalization are observed in various human cancers, suggesting functional inactivation.

Purpose of the Study:

  • To investigate the interaction between ING1 and 14-3-3 proteins.
  • To determine how this interaction affects ING1's subcellular localization and biological activity.
  • To elucidate the role of 14-3-3 proteins in regulating ING1 function in cancer.

Main Methods:

  • Bioinformatics analysis to identify potential binding sites between ING1 and 14-3-3 proteins.
  • Co-immunoprecipitation assays to confirm the interaction between p33(ING1b) and 14-3-3 proteins.
  • Cellular localization studies and functional assays measuring p21(Waf1) levels after UV-induced DNA damage.

Main Results:

  • A specific binding motif for 14-3-3 proteins was identified in the ING1 protein sequence.
  • The p33(ING1b) splicing isoform of ING1 interacts with 14-3-3 proteins, regulated by ING1 phosphorylation.
  • 14-3-3 binding causes p33(ING1b) to accumulate in the cytoplasm, inhibiting its ability to up-regulate p21(Waf1) following DNA damage.

Conclusions:

  • 14-3-3 proteins regulate the tumor suppressor ING1 by controlling its subcellular localization.
  • Phosphorylation-dependent interaction with 14-3-3 proteins sequesters p33(ING1b) in the cytoplasm, potentially contributing to cancer development.
  • Targeting the ING1-14-3-3 interaction could be a strategy to restore ING1 tumor suppressor activity.

More Related Videos

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

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.
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...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...