Related Experiment Video

Updated: Mar 13, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

8.0K

X-linked inhibitor of apoptosis-associated factor 1 regulates TNF receptor 1 complex stability

Boren Lin1, Da Xu1, Douglas W Leaman1

  • 1Department of Biological Sciences, The University of Toledo, OH, USA.

FEBS Letters
|November 4, 2016
PubMed

Insights

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) suppresses tumor necrosis factor (TNF)-alpha signaling. XAF1 negatively regulates NF-κB activation by disrupting key protein complex assembly in the TNF receptor pathway.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Immunology

Background:

  • X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a protein with a poorly understood role in cellular functions.
  • Tumor necrosis factor (TNF)-alpha signaling pathways are crucial in immune responses and cellular regulation.

Discussion:

  • This study investigates the function of XAF1 in TNF-alpha-induced signaling.
  • XAF1's role as a negative regulator of NF-κB activation is demonstrated through overexpression and gene silencing experiments.
  • The mechanism involves disrupting the TRADD/TRAF2/RIP1 complex formation downstream of the TNF receptor.

Key Insights:

  • XAF1 inhibits TNF-alpha-induced NF-κB activation.
  • XAF1 interacts with TRAF2, inhibiting its polyubiquitination and subsequent NF-κB activation.
  • XAF1 binds RIP1, disrupting the RIP1/TRADD association, thereby modulating TNF receptor signaling.

Outlook:

  • XAF1 acts as a feedback regulator in the TNF receptor signaling pathway.
  • Understanding XAF1's mechanism provides insights into controlling inflammatory and immune responses.
  • Further research can explore therapeutic strategies targeting XAF1 in diseases associated with aberrant TNF signaling.
Keywords:
Receptor interacting protein kinase 1XIAP associated factor 1inflammatory responsenuclear factor-kappa Btumor necrosis factortumor necrosis factor receptor-associated factor 2

More Related Videos

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

8.7K
Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

10.9K

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...
10.8K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
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...
9.2K
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...
9.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
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...
6.1K