USP16 Regulates the Stability and Function of LDL receptor by Deubiquitination

Li, Yongsheng; Rao, Yanbiao; Zhu, Hongtao; Jiang, Bingyuan; Zhu, Maoshu

doi:10.1536/ihj.20-043

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…Nuclear USP16 also deubiquitinates PLK1 for mitotic chromosome alignment and c-Myc in prostate cancer [ 45 , 46 ]. In the cytoplasm, USP16 deubiquitinates calcineurin for T cell maintenance [ 47 ], LDLR for coronary artery function [ 50 ], RPS27a for 40S ribosomal subunit biogenesis and maturation [ 31 ], and Tektin for male fertility [ 51 ]. USP16 also deubiquitinates proteins in oncogenic pathways, for example, IGF2BP3 in gallbladder cancer [ 48 ], whereas Ct-HBx inhibits the expression level of USP16 in hepatocellular carcinoma [ 40 ], revealing the intrinsic link to cancer development.…”

Section: Discussionmentioning

confidence: 99%

“…LDL is taken up by membrane scavenger receptors, including LDL receptor (LDLR) [ 63 ]. Through screening the siRNA library against the USP family of DUBs, USP16 was found to affect LDL the most [ 50 ] ( Figure 4 J). Subsequent studies revealed that USP16 does not regulate the transcription of LDLR but regulates its protein stability.…”

Section: The Substrates and Functions Of Usp16mentioning

confidence: 99%

“…Co-immunoprecipitation revealed that USP16 interacts with LDLR and deubiquitinates the receptor, thus protecting it against degradation ( Figure 4 J). These data suggest that USP16 intervention could be a potential strategy for ameliorating atherosclerosis and coronary artery diseases [ 50 ].…”

Section: The Substrates and Functions Of Usp16mentioning

confidence: 99%

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The Pleiotropic Ubiquitin-Specific Peptidase 16 and Its Many Substrates

Zheng

Chen

Guo

et al. 2023

Cells

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Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase that plays a role in the regulation of gene expression, cell cycle progression, and various other functions. It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. The strong connection to immune response and the fact that multiple oncogene products are substrates of USP16 suggests that USP16 may be a potential therapeutic target for the treatment of certain human diseases.

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Section: Discussionmentioning

confidence: 99%

Section: The Substrates and Functions Of Usp16mentioning

confidence: 99%

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The Pleiotropic Ubiquitin-Specific Peptidase 16 and Its Many Substrates

Zheng

Chen

Guo

et al. 2023

Cells

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“…On the other hand, USP16 is implicated in T-cell mediated immunity [ 65 ], and also in the LDL receptor stability and activity [ 66 ]. The latter function could have relevant implications in the piglets of the present study.…”

Section: Resultsmentioning

confidence: 99%

Hypothalamic transcriptome analysis reveals male-specific differences in molecular pathways related to oxidative phosphorylation between Iberian pig genotypes

et al. 2022

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The hypothalamus is implicated in controlling feeding and adiposity, besides many other physiological functions, and thus can be of great importance in explaining productive differences between lean and fatty pig breeds. The present study aimed to evaluate the hypothalamic transcriptome of pure Iberian (IBxIB) and Large White x Iberian crossbreds (IBxLW) at 60 days-old, produced in a single maternal environment. Results showed the implication of gender and genotype in the hypothalamic transcriptome, with 51 differentially expressed genes (DEGs) between genotypes and 10 DEGs between genders. Fourteen genotype by sex interactions were found, due to a higher genotype effect on transcriptome found in males. In fact, just 31 DEGs were identified when using only females but 158 using only males. A higher expression of genes related to mitochondrial activity in IBxIB male animals (ND3, ND4, ND5, UQCRC2 and ATP6) was found, which was related to a higher oxidative phosphorylation and greater reactive oxygen species and nitric oxide production. IBxLW male animals showed higher expression of SIRT3 regulator, also related to mitochondrial function. When females were analysed, such differences were not found, since only some differences in genes related to the tricarboxylic acid cycle. Thus, the results indicate a significant effect and interaction of the breed and the sex on the hypothalamic transcriptome at this early age.

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“…Ubiquitin carboxyl-terminal hydrolase 16 (USP16, also called UBPM), a widely expressed deubiquitinase, has been implicated to function in cell proliferation, division, and differentiation 11 , 12 . It specifically deubiquitinates H2A histones, and thereby regulates gene transcription and DNA repair 13 .…”

Section: Introductionmentioning

confidence: 99%

FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice

Tong,

Chen,

Chen

et al. 2023

Nat Commun

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Hepatic ischemia-reperfusion injury (IRI) is a common complication occurs during hepatic resection and transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Here, we aim to explore the role of fibroblast growth factor 18 (FGF18) in hepatic IRI. In this work, we find that Hepatic stellate cells (HSCs) secrete FGF18 and alleviates hepatocytes injury. HSCs-specific FGF18 deletion largely aggravates hepatic IRI. Mechanistically, FGF18 treatment reduces the levels of ubiquitin carboxyl-terminal hydrolase 16 (USP16), leading to increased ubiquitination levels of Kelch Like ECH Associated Protein 1 (KEAP1) and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, USP16 interacts and deubiquitinates KEAP1. More importantly, Nrf2 directly binds to the promoter of USP16 and forms a negative feedback loop with USP16. Collectively, our results show FGF18 alleviates hepatic IRI by USP16/KEAP1/Nrf2 signaling pathway in male mice, suggesting that FGF18 represents a promising therapeutic approach for hepatic IRI.

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USP16 Regulates the Stability and Function of LDL receptor by Deubiquitination

Cited by 7 publications

References 27 publications

The Pleiotropic Ubiquitin-Specific Peptidase 16 and Its Many Substrates

The Pleiotropic Ubiquitin-Specific Peptidase 16 and Its Many Substrates

Hypothalamic transcriptome analysis reveals male-specific differences in molecular pathways related to oxidative phosphorylation between Iberian pig genotypes

FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice

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