NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

Qiu, Beiying; Shi, Xiaohe; Wong, Ee Tsin; Lim, Joy; Bezzi, Marco; Low, D J H; Zhou, Qiling; Akıncılar, Semih Can; Lakshmanan, Manikandan; Swa, Hannah L. F.; Tham, Jill M.; Gunaratne, Jayantha; Cheng, Kenneth K.Y.; Hong, Wanjin; Lam, Karen Siu Ling; Ikawa, Masahito; Guccione, Ernesto; Xu, Aimin; Han, Weiping; Tergaonkar, Vinay

doi:10.1016/j.celrep.2014.05.030

Cited by 42 publications

(62 citation statements)

References 32 publications

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“…Genotypes of NWT and NKO mice were confirmed as described previously (Supplementary Figure S1)13. Alkaline injury was induced within a confined circular area ~2-mm in diameter in the central corneal region in NWT and NKO mice.…”

Section: Resultsmentioning

confidence: 90%

“…The transgenic mouse lines (NWT and NKO) were gifts from Dr Vinay Tergaonkar (IMCB), the Laboratory of NFκB Signaling, Singapore13. Genotypes of all NWT and NKO mice were confirmed (full-length gel image is presented in Supplementary Figure S1) (primary antibody: anti-NUCKS antibody; Abcam 1:200; corresponding secondary antibody: Cell Signaling, 1:1000).…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Poon

Jiang

Qin

et al. 2017

Sci Rep

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Corneal wound healing involves a complex cascade of cytokine-controlled cellular events, including inflammatory and angiogenesis responses that are regulated by transcriptional chromatin remodeling. Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate (NUCKS) is a key chromatin modifier and transcriptional regulator of metabolic signaling. In this study, we investigated the role of NUCKS in corneal wound healing by comparing its effects on corneal alkali burn in NUCKS knockout (NKO) and NUCKS wild-type (NWT) mice. Our data showed that following alkali-injury, inhibition of NUCKS (NKO) accelerated ocular resurfacing and suppressed neovascularization; the cytokine profile of alkali burned corneas in NKO mice showed suppressed expression of inflammation cytokines (IL1A & IL1B); upregulated expression of antiangiogenic factor (Pigment Epithelium-derived Factor; PEDF); and downregulated expression of angiogenic factor (Vascular Endothelial Growth Factor, VEGF); in vitro, following LPS-induced NFκB activation, NKO corneal cells showed reduced expression of IL6, IP10 and TNFα. In vitro, corneal epithelial cells showed reduced NF-κb activation on silencing of NUCKS and corresponding NFκB-mediated cytokine expression was reduced. Here, we illustrate that inhibition of NUCKS played a role in cytokine modulation and facilitated corneal recovery. This reveals a potential new effective strategy for ocular burn treatment.

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Section: Resultsmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Poon

Jiang

Qin

et al. 2017

Sci Rep

Self Cite

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“…More than 50 genetic loci associated with type 2 diabetes have been identified, thus explaining a modest fraction of heritability [16]. Environmental factors are also crucial for the development of this pathology, and type 2 diabetes and insulin resistance have been directly related to obesity and a sedentary lifestyle [10,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Differential control of muscle mass in type 1 and type 2 diabetes mellitus

Sala

Zorzano

2015

Cell. Mol. Life Sci.

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Diabetes mellitus--whether driven by insulin deficiency or insulin resistance--causes major alterations in muscle metabolism. These alterations have an impact on nutrient handling, including the metabolism of glucose, lipids, and amino acids, and also on muscle mass and strength. However, the ways in which the distinct forms of diabetes affect muscle mass differ greatly. The most common forms of diabetes mellitus are type 1 and type 2. Thus, whereas type 1 diabetic subjects without insulin treatment display a dramatic loss of muscle, most type 2 diabetic subjects show no changes or even an increase in muscle mass. However, the most commonly used rodent models of type 2 diabetes are characterized by muscle atrophy and do not mimic the features of the disease in humans in terms of muscle mass. In this review, we analyze the processes that are differentially regulated under these forms of diabetes and propose regulatory mechanisms to explain them.

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“…NUCKS1 protein is identi ed as one of the cell cycle-related proteins and participates in the response of DNA damage induction [8,15]. Previous studies had reported that NUCKS1 played a crucial role in the regulation of glucose homoeostasis and insulin signalling [16,17]. Besides, NUCKS1 had been shown to be a key transcriptional regulator and chromatin modi er and it could be a potential bio-marker for human diseases, including cancers and metabolic diseases [18].…”

Section: Discussionmentioning

confidence: 99%

NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

Zhang

et al. 2020

Preprint

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Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.

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NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

Cited by 42 publications

References 32 publications

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Differential control of muscle mass in type 1 and type 2 diabetes mellitus

NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

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