Biomaterial Database

Sustained early growth response gene 3 expression inhibits the survival of CD4/CD8 double-positive thymocytes. 2004

Hongkang Xi, and Gilbert J Kersh

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322, USA.

In the absence of selection, CD4+, CD8+ double-positive (DP) thymocytes will die after 3-4 days. The mechanism for regulating the life span of DP cells is unknown. Previously, we demonstrated that the zinc finger transcription factor, early growth response gene 3 (Egr3), promotes proliferation during the transition from double negative (DN) to DP. In this study we demonstrate a novel role for Egr3 in controlling DP thymocyte survival in mice. Constitutive transgenic expression of Egr3 in thymocytes increases apoptosis among DP cells and shortens their survival in vitro. In addition, DP cells in Egr3 transgenic mice have poor expression of TCRalpha, and based on the predominant usage of 3' Valpha and 5' Jalpha gene segments, the low level of TCRalpha expression is a result of DP death soon after the initiation of TCRalpha rearrangements. Constitutive transgenic expression of Egr3 results in poor expression of Bcl-x(L) and the thymic isoform of retinoic acid receptor-related orphan receptor gamma (RORgammat) in DP thymocytes, two molecules that are required in DP cells for normal life span. Egr3 expression induced by pre-TCR signals in nontransgenic mice is transient and returns to background levels before RORgammat or Bcl-x(L) is induced. The data support a model in which Egr3 must be transiently induced in response to pre-TCR signals, so that the expression of the prosurvival molecules, RORgammat and Bcl-x(L), can be elevated only after the proliferative signal provided by Egr3 has subsided.

UI	MeSH Term	Description	Entries
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011988	Receptors, Thyroid Hormone	Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.	Diiodotyrosine Receptors,Receptors, Diiodotyrosine,Receptors, Thyroxine,Receptors, Triiodothyronine,T3 Receptors,T4 Receptors,Thyroid Hormone Receptors,Thyroxine Receptors,Triiodothyronine Receptors,DIT Receptors,Diiodotyrosine Receptor,MIT Receptors,Monoiodotyrosine Receptors,Receptors, DIT,Receptors, MIT,Receptors, Monoiodotyrosine,Receptors, T3,Receptors, T4,T3 Receptor,T4 Receptor,Thyroid Hormone Receptor,Thyroxine Receptor
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013601	T-Lymphocytes	Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.	T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D015332	Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor	Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.	T-Cell Antigen Receptor alpha-Chain Gene Rearrangement,T-Lymphocyte Antigen Receptor alpha-Chain Gene Rearrangement,Gene Rearrangement, alpha-Chain T Cell Antigen Receptor,T Cell alpha-Chain Gene Rearrangement,T Lymphocyte alpha-Chain Gene Rearrangement,Gene Rearrangement, alpha Chain T Cell Antigen Receptor,T Cell Antigen Receptor alpha Chain Gene Rearrangement,T Cell alpha Chain Gene Rearrangement,T Lymphocyte Antigen Receptor alpha Chain Gene Rearrangement,T Lymphocyte alpha Chain Gene Rearrangement
D015704	CD4 Antigens	55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.	Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D016693	Receptors, Antigen, T-Cell, alpha-beta	T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.	Antigen Receptors, T-Cell, alpha-beta,T-Cell Receptors alpha-Chain,T-Cell Receptors beta-Chain,T-Cell Receptors, alpha-beta,TcR alpha-beta,Antigen T Cell Receptor, alpha Chain,Antigen T Cell Receptor, beta Chain,Receptors, Antigen, T Cell, alpha beta,T Cell Receptors, alpha beta,T-Cell Receptor alpha-Chain,T-Cell Receptor beta-Chain,T-Cell Receptor, alpha-beta,T Cell Receptor alpha Chain,T Cell Receptor beta Chain,T Cell Receptor, alpha beta,T Cell Receptors alpha Chain,T Cell Receptors beta Chain,TcR alpha beta,alpha-Chain, T-Cell Receptor,alpha-Chain, T-Cell Receptors,alpha-beta T-Cell Receptor,alpha-beta T-Cell Receptors,alpha-beta, TcR,beta-Chain, T-Cell Receptor,beta-Chain, T-Cell Receptors