Related Experiment Video

Updated: Apr 6, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
08:20

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol

Published on: December 30, 2016

21.9K

Cyclin-dependent kinase 5 represses Foxp3 gene expression and Treg development through specific phosphorylation of

Eric Lam1, Sung Hee Choi2, Tej K Pareek2

  • 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University Hospitals Rainbow Babies & Children's Hospital Center, The Angie Fowler Adolescent & Young Adult Cancer Institute, United States; The Case Comprehensive Cancer Center, Case Western Reserve University, United States; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, United States.

Molecular Immunology
|July 23, 2015
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) regulates T cell differentiation by controlling Foxp3 expression. Cdk5 phosphorylates Stat3, enabling its DNA binding to the Foxp3 gene, crucial for T cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase involved in T cell function.
  • Previous research indicated Cdk5 disruption ameliorates T cell-mediated neuroinflammation.

Purpose of the Study:

  • To investigate the novel role of Cdk5 in regulating Foxp3 expression in murine CD4(+) T cells.
  • To elucidate the molecular mechanism by which Cdk5 influences T cell differentiation.

Main Methods:

  • Analysis of Cdk5 activity in T cells.
  • Investigating the effect of Cdk5 disruption on IL-6 suppression of Foxp3.
  • Assessing Cdk5-mediated phosphorylation of Stat3 at Serine 727.
  • Evaluating Stat3 DNA binding to the Foxp3 gene enhancer II region.

Main Results:

  • Cdk5 disruption abrogates IL-6 suppression of Foxp3 expression in T cells.
  • Cdk5 phosphorylates Stat3 at Serine 727 in T cells.
  • This phosphorylation is essential for Stat3 DNA binding to the Foxp3 gene enhancer II region.

Conclusions:

  • Cdk5 plays a critical role in T cell differentiation.
  • Cdk5 regulates Foxp3 gene expression via Stat3 phosphorylation.
  • Cdk5 is a key regulator of T cell function and immune responses.
Keywords:
Cyclin dependent kinasePhosphorylationPost-translationalRegulatory T cellSignaling

More Related Videos

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

16.5K
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice07:17

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

10.5K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.0K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.4K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
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...
5.4K
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...
6.2K