{
  "id": 15915145,
  "title": "p66Shc mediates SUMO2-induced endothelial dysfunction",
  "url": "https://urgent.news/2026/10/21/p66shc-mediates-sumo2-induced-endothelial-dysfunction",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-21T00:00:00.000Z",
  "source": {
    "name": "eLife",
    "slug": "elife",
    "url": "https://elifesciences.org/articles/106344"
  },
  "original_language": "en",
  "account": "Sumoylation, a post-translational modification, can influence various physiological processes. Elevated sumoylation, particularly the binding of SUMO2/3 to proteins, is detrimental to vascular health. However, the underlying molecular mechanism remains unclear. We employed cell-based assays and mass spectrometry to demonstrate that p66Shc is a direct target of SUMO2, with SUMO2 modulating p66Shc function through lysine-81 modification. To assess the impact of SUMO2-p66ShcK81 on vascular function, we created Shc1 K81R mice and bred them with Ldlr-/- mice to induce hyperlipidemia. Next, we evaluated the effects of SUMO2-p66ShcK81-SUMO2ylation on endothelial cell signaling using mass spectrometry and Ingenuity Pathway Analysis. Our findings show that p66Shc mediates the effects of SUMO2 on endothelial cells. Mass spectrometry revealed that SUMO2 modified lysine-81 in the unique collagen homology-2 domain of p66Shc. SUMO2ylation increased phosphorylation at serine-36 and translocated p66Shc to the mitochondria, a step crucial for its oxidative function. Importantly, p66ShcK81R (sumoylation-deficient) was resistant to SUMO2-induced phosphorylation and mitochondrial translocation. Shc1 K81R mice exhibited resistance to endothelial dysfunction caused by SUMO2ylation and hyperlipidemia. Ingenuity Pathway Analysis identified multiple signaling pathways regulated by p66ShcK81-SUMO2ylation in endothelial cells, with JAK-STAT being a major pathway affected by SUMO2-p66ShcK81. Our results demonstrate that SUMO2-p66Shc signaling is a crucial regulator of vascular endothelial function, with p66ShcK81 acting as an upstream modifier regulating p66Shc signaling and mediating hyperlipidemia-induced endothelial dysfunction and oxidative stress.",
  "summary": "Sumoylation is a post-translational modification that can regulate different physiological functions. Increased sumoylation, specifically conjugation of SUMO2/3 (small ubiquitin-like modifier 2/3), is detrimental to vascular health. However, the molecular mechanism mediating this effect is poorly understood. We used cell-based assays and mass spectrometry to show that p66Shc is a direct target of…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}