Related Experiment Video

Updated: Jul 11, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

Retinoic acid- and bone morphogenetic protein 4-induced apoptosis in P19 embryonal carcinoma cells requires p27

M A Glozak1, M B Rogers

  • 1Department of Biology, University of South Florida, BSF119, 4202 E. Fowler Avenue, Tampa, Florida 33620, USA.

Experimental Cell Research
|August 2, 2001
PubMed

Insights

Retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) induce programmed cell death in P19 cells by increasing the Cdk inhibitor p27, leading to retinoblastoma (Rb) protein activation and apoptosis.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Programmed cell death (apoptosis) is crucial for embryonic development.
  • P19 embryonal carcinoma cells are a model system to study apoptosis.
  • Retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) can induce apoptosis in P19 cells.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which RA and BMP4 induce apoptosis in P19 cells.
  • To investigate the role of cell cycle proteins in RA- and BMP4-induced apoptosis.

Main Methods:

  • Treatment of P19 cells with RA and BMP4.
  • Analysis of cell cycle phase distribution.
  • Measurement of mRNA and protein levels of cyclins, Cdk inhibitor p27, and retinoblastoma (Rb) protein.
  • Inhibition of p27 using antisense oligonucleotides.

Main Results:

  • RA and BMP4 treatment increased G1 phase cells and induced apoptosis.
  • While cyclin D1 and D2 mRNA decreased, their protein levels remained unchanged.
  • RA and BMP4 induced p27 protein, which inhibited Cdk4 kinase activity.
  • p27 antisense oligonucleotides rescued cells from apoptosis.
  • Retinoblastoma (Rb) protein was induced and hypophosphorylated in apoptotic cells.

Conclusions:

  • RA and BMP4 induce apoptosis in P19 cells through the p27-mediated inhibition of Cdk4.
  • This leads to Rb hypophosphorylation and activation, ultimately promoting apoptosis.
  • p27 is a necessary mediator of RA- and BMP4-induced apoptosis.

More Related Videos

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies09:04

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Published on: April 22, 2017

Neurogenesis Using P19 Embryonal Carcinoma Cells07:46

Neurogenesis Using P19 Embryonal Carcinoma Cells

Published on: April 27, 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.
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...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...