Related Experiment Video

Updated: Apr 19, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K

The CDK4/CDK6 inhibitor PD0332991 paradoxically stabilizes activated cyclin D3-CDK4/6 complexes

Sabine Paternot1, Bianca Colleoni, Xavier Bisteau

  • 1a WELBIO and Institute of Interdisciplinary Research (IRIBHM) ; Université Libre de Bruxelles ; Campus Erasme; Brussels , Belgium.

Cell Cycle (Georgetown, Tex.)
|December 9, 2014
PubMed
Summary

The CDK4/6 inhibitor PD0332991 can paradoxically activate cyclin D3-CDK4/6 complexes, promoting cell cycle entry. This unexpected effect, dependent on p21 binding, requires careful assessment in clinical trials of this cancer therapy.

Keywords:
2D, 2-dimensionalBrdU, bromodeoxyuridineCAK, CDK-activating kinaseCDK, cyclin-dependent kinaseCDK4CDK6FBS, fetal bovine serumIP, immunoprecipitationPAGE, polyacrylamide gel electrophoresisPBS, phosphate buffer salinePD033, PD0332991PD0332991PalbociclibSDS, sodium dodecyl sulfateSEM, standard error of the meancell cycle-based tumor therapeuticscyclin D3p21pRb, retinoblastoma susceptibility protein

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

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

Published on: May 3, 2018

19.5K
Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk113:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

12.5K

Related Concept Videos

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...
6.3K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.7K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
7.1K
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.
137.4K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

3.1K