Deciphering the multifaceted roles of TET proteins in T-cell lineage specification and malignant transformation

Ageliki Tsagaratou1,2,3,4,5

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Immunological Reviews
|January 7, 2021
PubMed

Insights

TET proteins, crucial DNA demethylases, regulate T-cell development and cell fate by controlling gene expression. Understanding their role in T-cell lineage specification is key to cell identity and disease research.

Area of Science:

  • Epigenetics and Molecular Biology
  • Immunology
  • Developmental Biology

Background:

  • TET proteins are DNA demethylases that modify 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and other oxidized bases.
  • These modifications are critical for regulating gene expression and cell fate decisions during development.
  • TET proteins play a significant role in the development of various cell types, including T-cells.

Purpose of the Study:

  • To review the multifaceted roles of TET proteins in T-cell lineage specification.
  • To explore how TET proteins regulate gene expression during T-cell development, lineage commitment, function, and in disease contexts.
  • To discuss future research directions for understanding TET protein mechanisms in maintaining cell identity.

Main Methods:

  • This review synthesizes existing literature on TET proteins and T-cell biology.
  • It explores findings from genetic, biochemical, and epigenetic studies.
  • Focuses on the regulatory mechanisms of TET proteins in T-cell development and function.

Main Results:

  • TET proteins are essential for T-cell development and lineage specification.
  • They regulate gene expression programs critical for T-cell identity and function.
  • Dysregulation of TET proteins is implicated in T-cell related diseases.

Conclusions:

  • TET proteins are central regulators of T-cell lineage specification and function through epigenetic modifications.
  • Further research is needed to fully elucidate the precise mechanisms by which TET proteins fine-tune gene expression and maintain T-cell identity.
  • Understanding these mechanisms holds promise for therapeutic strategies in T-cell related disorders.

Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
14.1K
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...
4.9K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.1K
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...
9.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.4K