Related Experiment Video

Updated: Apr 19, 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

19.5K

The cyclin D1-CDK4 oncogenic interactome enables identification of potential novel oncogenes and clinical prognosis

Siwanon Jirawatnotai1, Samanta Sharma, Wojciech Michowski

  • 1a Department of Pharmacology; Faculty of Medicine Siriraj Hospital ; Mahidol University ; Bangkok , Thailand.

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

Insights

Researchers mapped the protein interactions of cyclin D1 and CDK4 in breast cancer cells. They identified BAIAPL21 as a potential oncogene and developed an Aggregate Expression Score (AES) for cancer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Overexpression of cyclin D1 and CDK4 is common in human cancers.
  • Understanding protein interactions is crucial for identifying cancer drivers and developing new therapies.

Purpose of the Study:

  • To construct the cyclin D1 and CDK4 protein interaction network in MCF7 breast cancer cells.
  • To identify novel CDK4 interactors and potential oncogenes.
  • To assess the prognostic value of cyclin D1 interactome expression in human cancers.

Main Methods:

  • Protein-protein interaction network construction using MCF7 cells.
  • Identification and validation of novel protein partners.
  • Integrative analysis of interactome data with somatic copy number alterations.
  • Assessment of BAIAPL21 oncogenic potential through overexpression studies.
  • Development and validation of an Aggregate Expression Score (AES).

Main Results:

  • Novel CDK4 protein partners, including FKBP5, were identified, with FKBP5 maintaining CDK4 levels.
  • BAIAPL21 was identified as a potential oncogene, showing increased expression in tumors and enhancing cancer cell growth and tumor formation in vivo.
  • The Aggregate Expression Score (AES) demonstrated prognostic value in ER-positive breast cancers.

Conclusions:

  • Protein interactome analysis is a valuable strategy for discovering novel oncogenes and improving cancer prognosis.
  • BAIAPL21 represents a potential therapeutic target and biomarker.
  • The AES provides a novel tool for predicting patient outcomes in specific breast cancer subtypes.
Keywords:
ACN, acetonitrileAES, aggregate expression scoreATCC, American type culture collectionCDK4DMEM, Dulbecco's Modified Eagle's mediumFBS, fetal bovine serumLC-MS/MS, liquid chromatography-tandem mass spectrometryPPI, protein-protein interactionRPMI, Roswell Park Memorial Institute mediumSCNA, somatic copy-number variationTCGA, the cancer genome atlasWB, immunoblottingbreast cancercyclin D1interactomeoncogenesoncogenic signaturesiFKBP4, FKBP4-specific small interfering RNAsiFKBP5, FKBP5-specific small interfering RNAsiRNA, small interfering RNAsicont, control small interfering RNAsicyclin D1, cyclin D1-specific small interfering RNA

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.9K

Related Concept Videos

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
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