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Anaphase Promoting Complex

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

Inhibition of Cdk Activity

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...

Positive Regulator Molecules

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.

Positive Regulator Molecules

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

Abnormal Proliferation

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...

Negative Regulator Molecules

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.

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Related Experiment Video

Updated: Nov 23, 2025

Xenopus laevis as a Model to Identify Translation Impairment

Xenopus laevis as a Model to Identify Translation Impairment

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Augmenting E Protein Activity Impairs cDC2 Differentiation at the Pre-cDC Stage.

Sandra Bajana¹, Kevin Thomas¹, Constantin Georgescu²

¹Program in Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.

Frontiers in Immunology

|January 4, 2021

Summary

Temporal control of E protein activity is crucial for balanced dendritic cell (DC) differentiation. Overactivating E proteins with a mutant (ET2) reduced conventional DC subset 2 (cDC2) development and altered transcription factor expression, shifting cDC2s towards a cDC1-like profile.

Keywords:

E protein IRF4 IRF8 cDC1 cDC2 pre-cDC

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Area of Science:

Immunology
Developmental Biology
Molecular Biology

Background:

Dendritic cell (DC) development relies on transcription factor networks.
E proteins and their inhibitors, ID proteins, are key regulators of DC differentiation.
Previous studies highlighted the essential roles of E and ID proteins in DC development.

Purpose of the Study:

To investigate the importance of temporal E protein activity control in maintaining balanced differentiation of conventional DC (cDC) subsets, specifically cDC1 and cDC2.
To utilize a gain-of-function approach by expressing a dominant-active E protein mutant (ET2).

Main Methods:

Expression of a dominant-active E protein mutant (ET2) in hematopoietic progenitors.
Analysis of DC subset development in vivo (spleen, lung) and in vitro (bone marrow-derived DC cultures).
Assessment of transcription factor expression (IRF8, IRF4) and global transcriptomes in cDC subsets.

Main Results:

ET2 expression at the progenitor stage significantly reduced cDC2 precursors and mature cDC2s in multiple tissues and cultures.
ET2 expression led to aberrant upregulation of IRF8 and downregulation of IRF4 in cDC2s.
Transcriptomic analysis revealed a partial shift of cDC2 transcriptional profiles towards those of cDC1.

Conclusions:

Precise temporal control of E protein activity is essential for the balanced differentiation of cDC1 and cDC2 subsets.
Aberrant E protein activity, as induced by ET2, impairs cDC2 differentiation, potentially through altered IRF8/IRF4 expression and transcriptional reprogramming.