X-Linked Inhibitor Of Apoptosis (XIAP) And How To Inhibit XIAP

X-Linked Inhibitor Of Apoptosis (XIAP)

 
 

X-Linked Inhibitor Of Apoptosis (XIAP) has shown to play a role in cancer, longevity, inflammatory resistance, and more.

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Basics Of XIAP

X-Linked Inhibitor Of Apoptosis (XIAP) plays a role in cell death. R

Dysregulation of cell death (apoptosis) and related signaling pathways are involved in growth and proliferation of malignant cells and are critical processes in sustaining the unlimited progression and survival in cancer cells. R

Benefits Of XIAP Activation

1. May Improve Longevity And Have Antioxidant Effects

Increasing pro-survival genes (e.g. Xiap and Bcl-2) may improve cell survival. R

For example, Alpha Lipoic Acid (ALA) may help increase antioxidant levels by XIAP-mediated pathways. R

2. Infections And Inflammatory Disease

X-Linked Lymphoproliferative Disease Type 2 (XLP-2) is a primary immunodeficiency caused by the loss of XIAP. R R

People with XLP-2 have increased risk to potentially fatal infections, such as Epstein-Barr Virus (EBV) or Crohn's Disease (CD)-related infections leading to Inflammatory Bowel Disease (IBD). R R R

Increasing XIAP may benefit XLP-2 and related conditions. R

3. Plays A Role In Wilson's Disease And Copper Toxicity

XIAP levels are greatly reduced by Copper accumulation in Wilson's Disease (WD) and other high copper toxicosis disorders. R

XIAP Promoters

 
 

Natural XIAP Inducers:

Other:

  • COMP R
  • IL-6 R
  • Paclitaxel R
  • TGF-beta R

Benefits Of XIAP Inhibition

1. Fights Cancer

 
 

Overexpression of XIAP has been seen in Cancer. R

Inhibiting XIAP may help induce apoptosis in cancer cells. R R

2. Helps Overcome Chemoresistance

XIAP protein and mRNA levels have been associated with Chemoresistance and poor clinical outcome in cancer patients. R R R

Inhibiting XIAP expression can help overcome chemoresistance. R R R

3. Improves Stroke And TBI Outcome

XIAP inhibition may protect against damage from a Traumatic Brain Injury (TBI). R

For example, embelin can protect against delayed neuronal death after brain trauma (via inhibition of NFkB, p53 and XIAP). R

4. May Improve HIV Treatment

XIAP mRNA have shown to be elevated in Chinese HIV-1-infected patients. R

Reducing XIAP may help slow down HIV progression. R

XIAP Inhibitors

 
 

Natural XIAP Inhibitors:

Other

  • AEG35156 R
  • Chetomin (mycotoxin) R
  • Hsp70 inhibition R
  • HSP72 R
  • Metformin R
  • YM155 R

Caveats

IAP antagonists may promote metastasis. R

XIAP may be sex specific in stroke - XIAP protected female brains from deleterious effects of early HI injury, while elimination of this protection via XIAP inhibitor embelin exacerbated both damage and behavioural deficits, with no effect on HI males. R

Mechanism Of Action

Simple:

  • Increases Akt R
  • Increases Survivin R
  • Reduces Caspase 3 R
  • Reduces Caspase 7 R
  • Reduces Caspase 9 R
  • Reduces COMMD1 R
  • Reduces SMAC R

Advanced:

  • This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme.
  • This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7.
  • XIAP antagonism blocks NOD2-mediated inflammatory signaling and cytokine production by interfering with XIAP-RIP2 binding, which removes XIAP from its ubiquitination substrate RIP2. R
  • XIAP gene expression and function is positively regulated by exposure to the three TGF-beta isoforms in a Smad-dependent manner, similar to constitutive XIAP gene expression which depends on autocrine TGF-beta/Smad signalling. R
  • TGFβ/Smad3/IRS-1 signaling axis regulates expression of cyclin D1 and XIAP, which may contribute to TGFβ/Smad3/IRS-1-mediated cell cycle progression and survival. R
  • Cytosolic XIAP feeds back to mitochondria to impair Smac release. R

Genetics

XIAP

    rs12687176

    rs12838858

    rs17334739

    rs2355676

    rs28382699

    rs28382721

    rs28382722

    rs28382723

    rs28382739

    rs28382740

    rs28382741

    rs28382742

    rs5956578

    rs5956583

    rs5958318

    rs5958338

    More Research

    • A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein-Barr virus-specific T cells. R
    • X-Linked Lymphoproliferative Syndrome and Common Variable Immunodeficiency May Not Be Differentiated by SH2D1A and XIAP/BIRC4 Genes Sequence Analysis R
    • Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease R