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Cullin-Ring ubiquitin ligases in kidney health and disease

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

Current Opinion in Nephrology and Hypertension: September 2019 - Volume 28 - Issue 5 - p 490–497
doi: 10.1097/MNH.0000000000000527
MOLECULAR CELL BIOLOGY AND PHYSIOLOGY OF SOLUTE TRANSPORT: Edited by Vivek Bhalla and Alan C. Pao
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Purpose of review Members 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 findings Cullin 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.

Summary Cullins form a large and diverse family of E3 ubiquitin ligases that are likely to have many important functions in the kidney.

Division of Nephrology and Hypertension, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA

Correspondence to James A. McCormick, Oregon Health and Science University, 2730 Moody Avenue CL3NR, Portland, OR 97201, USA. Tel: +1 503 494 3980; e-mail: mccormij@ohsu.edu

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