Autophagy Induced by Proteasomal DUB Inhibitor NiPT Restricts NiPT-Mediated Cancer Cell Death

Chen, Jinghong; Chen, Xin; Xu, Dacai; Yang, Li; Yang, Zhenjun; Yang, Qianqian; Ding, Yan; Zhang, Peiquan; Feng, Du; Liu, Jinbao

doi:10.3389/fonc.2020.00348

Cited by 9 publications

(6 citation statements)

References 58 publications

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“…Chronic lung diseases, such as lung cancer and pneumonia, are associated with nickel exposure, which activates the ULK1/Beclin‐1 autophagy cascade in pulmonary bronchial epithelial cells by inhibiting mTOR (Huang et al, 2016). Studies have shown that hexokinase Nrf2, HK2, and STAT3 are also involved in nickel‐induced autophagy in pulmonary bronchial epithelial cells (Chen et al, 2020; Son et al, 2017).…”

Section: Regulation Of Autophagy By Other Metalsmentioning

confidence: 99%

Transition metals and metal complexes in autophagy and diseases

Luo

Huang

et al. 2021

Journal Cellular Physiology

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Transition metals refer to the elements in the d and ds blocks of the periodic table. Since the success of cisplatin and auranofin, transition metal‐based compounds have become a prospective source for drug development, particularly in cancer treatment. In recent years, extensive studies have shown that numerous transition metal‐based compounds could modulate autophagy, promising a new therapeutic strategy for metal‐related diseases and the design of metal‐based agents. Copper, zinc, and manganese, which are common components in physiological pathways, play important roles in the progression of cancer, neurodegenerative diseases, and cardiovascular diseases. Furthermore, enrichment of copper, zinc, or manganese can regulate autophagy. Thus, we summarized the current advances in elucidating the mechanisms of some metals/metal‐based compounds and their functions in autophagy regulation, which is conducive to explore the intricate roles of autophagy and exploit novel therapeutic drugs for human diseases.

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Section: Regulation Of Autophagy By Other Metalsmentioning

confidence: 99%

Transition metals and metal complexes in autophagy and diseases

Luo

Huang

et al. 2021

Journal Cellular Physiology

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“…It has also been reported that the DUB inhibitor NiPT, which also blocks both Uchl5 and Usp14, induces autophagy in A549 and NCI-H1299 lung cancer cell lines (J. Chen et al, 2020). In agreement with a previous study by Kim et al (E. Kim et al, 2018), we demonstrate that IU1 treatment impairs autophagy, as detected by increased GFP/RFP ratio as well as accumulation of LC3-II and p62.…”

Section: Discussionmentioning

confidence: 94%

Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy

Jha,

Pispa,

Holmberg

2024

Preprint

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The autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interact in vivo. Here, we have investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4, a regulator of proteasome activity, affects autophagy in human cells and in various tissues in a multicellular organism. We have used the established GFP-LC3-RFP-LC3ΔG autophagy reporter HeLa cell line and show that downregulation of Uchl5 by siRNA reduces autophagy, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. Exposing Caenorhabditis elegans carrying the autophagy reporter mCherry::GFP::LGG-1 to ubh-4 or usp-14 RNAi, or to their pharmacological inhibitors, results in diverse effects regarding the numbers of autophagosomes and autolysosomes in the intestine, hypodermal seam cells and the pharynx. Our results reveal that the proteasome-associated DUBs Uchl5/UBH-4 and Usp14 affect autophagy in a differential tissue manner. A deeper insight into the interplay between UPS and ALP in various tissues in vivo has the potential to promote development of therapeutic approaches for disorders associated with proteostasis dysfunction.

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“…Among the DEPs, ABRAXAS2, also known as ABRO1, is a scaffold protein that recruits a variety of peptides to assemble BRCC36 isopeptide complex (BRISC) deubiquitinating enzyme (DUB) complexes. It has been shown that inhibitors of DUBs can induce autophagy and thereby inhibit cell death [57]. The BRISC enzyme has deubiquitination activity and consists of four known subunits: MERIT40; BRE, which is expressed in the brain and reproductive organs; BRCA1/BRCA2 complex, subunit 3 (BRCC3); and ABRO1 [58].…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Analysis Using Data‐Independent Acquisition Mass Spectrometry: New Epidermal Proteins That Reveal Sex Differences in the Aging Process

Chen

Zhang

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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The development of mass spectrometry has provided a method with extremely high sensitivity and selectivity that can be used to identify protein biomarkers. Epidermal proteins, lipids, and cornified envelopes are involved in the formation of the skin epidermal barrier. The epidermal protein composition changes with age. Therefore, quantitative proteomic changes may be indicative of skin aging. We sought to utilize data-independent acquisition mass spectrometry for noninvasive analysis of epidermal proteins in healthy Chinese individuals of different age groups and sexes. In our study, we completed high-throughput protein detection, analyzed protein differences with MaxQuant software, and performed statistical analyses of the proteome. We obtained interesting findings regarding ceruloplasmin (CP), which exhibited significant differences and is involved in ferroptosis, a signaling pathway significantly associated with aging. There were also several proteins that differed between sexes in the younger group, but the sex differences disappeared with aging. These proteins, which were associated with both aging processes and sex differences, are involved in signaling pathways such as apoptosis, oxidative stress, and genomic stability and can serve as candidate biomarkers for sex differences during aging. Our approach for noninvasive detection of epidermal proteins and its application to accurately quantify protein expression can provide ideas for future epidermal proteomics studies.

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Autophagy Induced by Proteasomal DUB Inhibitor NiPT Restricts NiPT-Mediated Cancer Cell Death

Cited by 9 publications

References 58 publications

Transition metals and metal complexes in autophagy and diseases

Transition metals and metal complexes in autophagy and diseases

Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy

Noninvasive Analysis Using Data‐Independent Acquisition Mass Spectrometry: New Epidermal Proteins That Reveal Sex Differences in the Aging Process

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