Related Experiment Video

Updated: Aug 23, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis

Mario Schiffer1, Peter Mundel, Andrey S Shaw

  • 1Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10461, USA.

The Journal of Biological Chemistry
|June 24, 2004
PubMed

Insights

CD2-associated protein (CD2AP) deficiency impairs podocyte survival by promoting TGF-beta1-induced apoptosis. This adaptor protein is crucial for activating pro-survival pathways, preventing kidney disease progression in mice.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • CD2-associated protein (CD2AP) is vital for T cell receptor signaling and maintaining podocyte health.
  • CD2AP deficiency in mice leads to nephrotic syndrome and renal failure due to glomerulosclerosis.

Purpose of the Study:

  • To investigate the role of CD2AP in podocyte apoptosis and its relationship with transforming growth factor-beta1 (TGF-beta1) signaling.
  • To elucidate the mechanism by which CD2AP influences TGF-beta1-mediated survival and apoptotic pathways in podocytes.

Main Methods:

  • Analysis of CD2AP-deficient (CD2AP-/-) and wild-type (CD2AP+/+) mice models.
  • In vitro studies using conditionally immortalized podocytes derived from CD2AP-/- and CD2AP+/+ mice.
  • Assessment of TGF-beta1-induced apoptosis and activation of key signaling pathways (PI3K/AKT, ERK1/2, p38 MAPK).

Main Results:

  • Increased TGF-beta1 expression and podocyte apoptosis were observed in CD2AP-/- mice preceding glomerulosclerosis.
  • CD2AP-/- podocytes exhibited heightened susceptibility to TGF-beta1-induced apoptosis, which was reversed by CD2AP reconstitution.
  • CD2AP deficiency selectively impaired TGF-beta1-induced activation of anti-apoptotic PI3K/AKT and ERK1/2 pathways, while enhancing pro-apoptotic p38 MAPK signaling.

Conclusions:

  • CD2AP acts as a critical mediator for selective activation of TGF-beta1-induced survival pathways and repression of apoptosis in podocytes.
  • Functional impairment of CD2AP contributes to TGF-beta1-induced podocyte apoptosis, representing an early pathogenic mechanism in focal-segmental glomerulosclerosis development.

More Related Videos

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

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 are of three kinds RI, RII, and RIII. The RI...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...