Cullin-Ring ubiquitin ligases in kidney health and disease

Ryan J. Cornelius, Mohammed Z. Ferdaus, Jonathan W. Nelson, James A. Mccormick

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Purpose of reviewMembers of the Cullin family act as scaffolds in E3 ubiquitin ligases and play a central role in mediating protein degradation. Interactions with many different substrate-binding adaptors permit Cullin-containing E3 ligases to participate in diverse cellular functions. In the kidney, one well established target of Cullin-mediated degradation is the transcription factor Nrf2, a key player in responses to oxidative stress. The goal of this review is to discuss more recent findings revealing broader roles for Cullins in the kidney.Recent findingsCullin 3 acts as the scaffold in the E3 ligase regulating Nrf2 abundance, but was more recently shown to be mutated in the disease familial hyperkalemic hypertension. Studies seeking to elucidate the molecular mechanisms by which Cullin 3 mutations lead to dysregulation of renal sodium transport will be discussed. Disruption of Cullin 3 in mice unexpectedly causes polyuria and fibrotic injury suggesting it has additional roles in the kidney. We will also review recent transcriptomic data suggesting that other Cullins are also likely to play important roles in renal function.SummaryCullins form a large and diverse family of E3 ubiquitin ligases that are likely to have many important functions in the kidney.

Original languageEnglish (US)
Pages (from-to)490-497
Number of pages8
JournalCurrent opinion in nephrology and hypertension
Volume28
Issue number5
DOIs
StatePublished - Sep 1 2019

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Keywords

  • Cullin
  • kidney fibrosis
  • renal carcinoma
  • ubiquitination

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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