Zeta-crystallin: a moonlighting player in cancer

Lulli, Matteo; Nencioni, Daniele; Papucci, Laura; Schiavone, Nicola

doi:10.1007/s00018-019-03301-3

Cited by 16 publications

(20 citation statements)

References 123 publications

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“…CRYZ has been previously reported to be expressed in both eye lens and other tissues [14]. In tissues out of the lens, the kidney has the most abundant CRYZ expression.…”

Section: Discussionmentioning

confidence: 97%

“…Unlike most of other crystallins, CRYZ is endowed with enzyme and nucleic acid-binding activities [14]. As an enzyme, CRYZ is structurally related to alcohol dehydrogenase [4] but functionally related to NADPH:quinone oxidoreductase (QOR) [19].…”

Section: Discussionmentioning

confidence: 99%

“…It consists of ζ (zeta), λ (lambda), ρ (rho), η (eta), τ (tau), μ (mu), ω (omega), ι (iota), υ (ypsilon), ɛ (epsilon), and δ (delta) crystallins, important for both eye lens and other tissues [6]. Among phylogenetically restricted crystallins, crystallin ζ (CRYZ) is expressed in the lens and many tissues out of the lens [14], suggesting CRYZ may play an important role in many physiological processes.…”

Section: Introductionmentioning

confidence: 99%

“…Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00424-020-02456-4) contains supplementary material, which is available to authorized users. moonlighting protein with NADPH: quinone oxidoreductase and mRNA stabilizing activity [14]. As an enzyme, CRYZ is structurally related to alcohol dehydrogenase [4] but functionally related to NADPH:quinone oxidoreductase (QOR) [19].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the lens, CRYZ is highly expressed in the kidney, where it may play an important role in regulating renal function [14]. It has been reported that CRYZ increases glutaminolysis via binding and stabilizing glutaminase (GLS) mRNA to increase NH4 + production and secretion and HCO3 − biosynthesis and reabsorption in response to acidosis in the proximal tubules [24].…”

Section: Introductionmentioning

confidence: 99%

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Activation of farnesoid X receptor (FXR) induces crystallin zeta expression in mouse medullary collecting duct cells

Alam

Luan

Gul

et al. 2020

Pflugers Arch - Eur J Physiol

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Crystallin zeta (CRYZ) is a phylogenetically restricted water-soluble protein and provides cytoprotection against oxidative stress via multiple mechanisms. Increasing evidence suggests that CRYZ is high abundantly expressed in the kidney where it acts as a transacting factor in increasing glutaminolysis and the Na + /K + /2Clcotransporter (BSC1/NKCC2) expression to help maintain acid-base balance and medullary hyperosmotic gradient. However, the mechanism by which CRYZ is regulated in the kidney remains largely uncharacterized. Here, we show that CRYZ is a direct target of farnesoid X receptor (FXR), a nuclear receptor important for renal physiology. We found that CRYZ was ubiquitously expressed in mouse kidney and constitutively expressed in the cytoplasm of medullary collecting duct cells (MCDs). In primary cultured mouse MCDs, CRYZ expression was significantly upregulated by the activation and overexpression of FXR. FXR-induced CRYZ expression was almost completely abolished in the MCD cells with siRNA-mediated FXR knockdown. Consistently, treatment with FXR agonists failed to induce CRYZ expression in the MCDs isolated from mice with global and collecting duct-specific FXR deficiency. We identified a putative FXR response element (FXRE) on the CRYZ gene promoter. The luciferase reporter and ChIP assays revealed that FXR can bind directly to the FXRE site, which was further markedly enhanced by FXR activation. Furthermore, we found CRYZ overexpression in MCDs significantly attenuated hypertonicity-induced cell death possibly via increasing Bcl-2 expression. Collectively, our findings demonstrate that CRYZ is constitutively expressed in renal medullary collecting duct cells, where it is transcriptionally controlled by FXR. Given a critical role of FXR in MCDs, CRYZ may be responsible for protective effect of FXR on the survival of MCDs under hypertonic condition during dehydration.

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“…CRYZ has been previously reported to be expressed in both eye lens and other tissues [14]. In tissues out of the lens, the kidney has the most abundant CRYZ expression.…”

Section: Discussionmentioning

confidence: 97%