Related Experiment Video

Updated: Jun 22, 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

C-terminal fragment of transforming growth factor beta-induced protein (TGFBIp) is required for apoptosis in human

Rogelio Zamilpa1, Rajesha Rupaimoole, Clyde F Phelix

  • 1Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.

Matrix Biology : Journal of the International Society for Matrix Biology
|June 10, 2009
PubMed

Insights

Transforming growth factor beta-induced protein (TGFBIp) fragmentation, particularly the EPDIM sequence in its C-terminus, triggers apoptosis. This C-terminal fragment is key to TGFBIp

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Transforming growth factor beta-induced protein (TGFBIp) is secreted extracellularly and its C-terminal fragmentation is linked to apoptosis.
  • The precise C-terminal region responsible for TGFBIp's pro-apoptotic activity and its interaction with integrins remains unclear.
  • Previous studies suggest the final 166 amino acids of TGFBIp contain pro-apoptotic properties.

Purpose of the Study:

  • To investigate if the pro-apoptotic property of TGFBIp depends on its final 69 amino acids, including integrin-binding sequences.
  • To determine the specific C-terminal sequences essential for TGFBIp-induced apoptosis.
  • To elucidate the role of integrin-binding sequences (EPDIM and RGD) in TGFBIp-mediated apoptosis.

Main Methods:

  • MG-63 osteosarcoma cells were treated with transforming growth factor (TGF)-beta1 to increase TGFBIp expression.
  • Apoptosis levels were measured following TGFBIp overexpression, addition of purified TGFBIp, and treatment with recombinant TGFBIp fragments.
  • Mass spectrometry analyzed TGFBIp fragmentation, and site-directed mutagenesis altered integrin-binding sequences (EPDIM, RGD).

Main Results:

  • TGF-beta1 treatment increased TGFBIp expression and apoptosis; this was blocked by an anti-TGFBIp antibody.
  • Overexpression of TGFBIp and addition of exogenous TGFBIp dose-dependently increased apoptosis.
  • Truncated TGFBIp lacking C-terminal integrin-binding sequences did not induce apoptosis, whereas a fragment of the final 69 amino acids did; mutation of the EPDIM sequence abolished apoptosis.

Conclusions:

  • The pro-apoptotic activity of TGFBIp is mediated by its C-terminal fragment, specifically the final 69 amino acids.
  • The integrin-binding sequence EPDIM within the C-terminus is critical for inducing apoptosis.
  • TGFBIp-induced apoptosis likely involves interactions between its C-terminus and cellular integrins.

More Related Videos

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos06:57

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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 rapamycin-insensitive companion...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...