Deciphering the SUMO code in the kidney

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.

• Publication year

  2018

• Venue

  Journal of Cellular and Molecular Medicine

• Publication date

  2018-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/jcmm.14021PMID 30506859PMCID 6349152
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Halting renal fibrosis: an unexpected role for mTORC2 signaling.

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  2014cited by this paper
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• Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis.

  2013cited by this paper
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  2012cited by this paper
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• Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity

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• SUMO, hypoxia and the regulation of metabolism.

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• Renal Parenchymal Hypoxia, Hypoxia Response and the Progression of Chronic Kidney Disease

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