Related Experiment Video

Updated: Jan 26, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

8.0K

Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation

Maksym Tsytlonok1, Hugo Sanabria2,3, Yuefeng Wang4,5

  • 1VIB Center for Structural Biology, Vrije Universiteit Brussel, Pleinlaan, 2 1050, Brussels, Belgium.

Nature Communications
|April 13, 2019
PubMed

Insights

p27Kip1, a disordered protein, uses intrinsic flexibility to integrate signals for cell cycle progression. This flexibility allows kinases to phosphorylate p27, triggering its degradation and enabling cell division.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • p27Kip1 is an intrinsically disordered protein (IDP) that regulates cell cycle arrest by inhibiting cyclin-dependent kinase (Cdk)/cyclin complexes.
  • Phosphorylation of p27Kip1 on specific residues triggers its degradation, allowing cell division to proceed.

Purpose of the Study:

  • To investigate the role of p27Kip1 intrinsic dynamics in integrating signaling inputs.
  • To elucidate the mechanism by which p27Kip1 phosphorylation leads to cell cycle progression.

Main Methods:

  • Integrated biophysical approaches were employed.
  • The study focused on the interactions of Cdk2/cyclin A-bound p27Kip1 with tyrosine kinases.

Main Results:

  • Cdk2/cyclin A-bound p27Kip1 adopts transient conformations accessible to BCR-ABL and Src kinases.
  • These kinases phosphorylate specific tyrosine residues (Y88, Y74) on p27Kip1, promoting T187 phosphorylation and degradation.
  • Intrinsic flexibility of p27Kip1 enables signal integration and regulation of Cdk2 activity and cell cycle progression.

Conclusions:

  • Intrinsic dynamics of intrinsically disordered proteins (IDPs) are crucial for signaling in multi-component assemblies.
  • This mechanism of signaling by IDPs can be dysregulated in human diseases.
  • p27Kip1 flexibility allows it to act as a signaling hub, linking kinase activity to cell cycle control.

More Related Videos

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations10:54

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

Published on: September 17, 2012

11.0K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.5K

Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
134.9K
Hormonal Regulation of the Menstrual Cycle01:22

Hormonal Regulation of the Menstrual Cycle

The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
1.5K
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.
38.3K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.8K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.0K