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Ymer acts as a multifunctional regulator in nuclear factor-κB and Fas signaling pathways

Tadasuke Tsukiyama1, Mayuko Matsuda-Tsukiyama, Miyuki Bohgaki

  • 1Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

Molecular Medicine (Cambridge, Mass.)
|February 15, 2012
PubMed

Insights

Ymer regulates immune responses by modulating nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Ymer transgenic mice show altered immune cell function and disease resistance, indicating its complex role in cellular signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Nuclear factor-kappa B (NF-κB) transcription factors control inflammation, oncogenesis, and apoptosis.
  • A20 is crucial for terminating NF-κB signaling.
  • Ymer was previously shown to interact with A20, leading to receptor-interacting protein (RIP) degradation and NF-κB attenuation.

Purpose of the Study:

  • To investigate the function of Ymer in regulating various signaling pathways, including NF-κB.
  • To analyze the impact of Ymer overexpression on immune responses and disease models using Ymer transgenic (Ymer Tg) mice.

Main Methods:

  • Utilized Ymer transgenic (Ymer Tg) mice to study Ymer's function.
  • Stimulated Ymer Tg and wild-type mice with tumor necrosis factor-alpha (TNF-α), polyI:C, and lipopolysaccharide (LPS).
  • Assessed immune responses including NF-κB and mitogen-activated protein kinase (MAPK) activation, cell proliferation, cytokine production, septic shock, glomerulonephritis, and Fas-mediated cell death.

Main Results:

  • Ymer Tg mice displayed impaired immune responses (NF-κB, MAPK activation, proliferation, cytokine production) upon TNF-α, polyI:C, or LPS stimulation.
  • Ymer Tg mice showed increased resistance to LPS-induced septic shock.
  • Ymer transgene inhibited glomerulonephritis onset in lpr/lpr mice and strongly induced Fas-mediated cell death in liver cells.
  • Ymer acts as a regulator downstream of several receptors, functioning in a pathway-dependent manner.

Conclusions:

  • Ymer plays a significant role in regulating immune responses and cellular signaling.
  • Ymer's function is context-dependent, acting as both a positive and negative regulator.
  • Ymer influences inflammatory and apoptotic pathways, impacting disease susceptibility and progression.

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