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<p>The balance between SUMOylation and deSUMOylation critically regulate cellular apoptosis, with SUMO-modified proteins implicated in ischemia/hypoxia injury. However, the specific contributions of SUMO-conjugated proteins in renal ischemia-reperfusion injury (IRI) remain poorly defined. SUMOylation in IRI was investigated Using proximal tubular-specific <i>Senp3</i> conditional knockout (CKO) mice. While SENP3-deficiency did not induce tubular injury under basal conditions, its significantly attenuated renal damage following IRI. SUMOylation conferred protection against apoptosis in renal tubular epithelia cells during ischemia/hypoxia. Mass spectrometry revealed arginosuccinate synthase 1 (ASS1) as a key SUMO2/3 target (modified at K239 and K310) in IRI progression. Mechanistically, SENP3-mediated deSUMOylation promoted ASS1 nuclear accumulation in post-IRI tubular epithelial cells, subsequently activating the intrinsic apoptosis pathway via p53-dependent transcriptional upregulation. These findings nominate the SENP3-ASS1-p53 axis as a potential therapeutic target for renal IRI.</p><p></p>

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SENP3 promotes renal tubular epithelial cell apoptosis after ischemia-reperfusion injury via ASS1 deSUMOylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月5日

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  • Hongju Wang,
  • Cui Gao,
  • Jingjuan Yang,
  • Lini Jin,
  • Longlong Wu,
  • Qian Zhang,
  • Xin Fang,
  • Hong Pan,
  • Huijuan Wu,
  • Pattarin Tangtanatakul,
  • Weiqiang Lin,
  • Yi Yang

摘要

The balance between SUMOylation and deSUMOylation critically regulate cellular apoptosis, with SUMO-modified proteins implicated in ischemia/hypoxia injury. However, the specific contributions of SUMO-conjugated proteins in renal ischemia-reperfusion injury (IRI) remain poorly defined. SUMOylation in IRI was investigated Using proximal tubular-specific Senp3 conditional knockout (CKO) mice. While SENP3-deficiency did not induce tubular injury under basal conditions, its significantly attenuated renal damage following IRI. SUMOylation conferred protection against apoptosis in renal tubular epithelia cells during ischemia/hypoxia. Mass spectrometry revealed arginosuccinate synthase 1 (ASS1) as a key SUMO2/3 target (modified at K239 and K310) in IRI progression. Mechanistically, SENP3-mediated deSUMOylation promoted ASS1 nuclear accumulation in post-IRI tubular epithelial cells, subsequently activating the intrinsic apoptosis pathway via p53-dependent transcriptional upregulation. These findings nominate the SENP3-ASS1-p53 axis as a potential therapeutic target for renal IRI.