ArticleCancers2021
The Carcinogen Cadmium Activates Lysine 63 (K63)-Linked Ubiquitin-Dependent Signaling and Inhibits Selective Autophagy.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Chronic exposure to low levels of glyphosate and metals induces kidney dysfunction.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Roles of autophagy in sepsis-induced myocardial dysfunction: a comprehensive review.American journal of translational research · 2026Review
- Regulatory roles of E3 ubiquitin ligase RNF128 in inflammatory diseases and tumors.Journal of Cancer · 2026Review
- 5'-Methylthioadenosine Metabolic Reprogramming Drives H3K79 Monomethylation-Mediated PAK2 Upregulation to Promote Cadmium-Induced Breast Cancer Progression by Impairing Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Cd stabilizes HIF-1α under normoxic conditions via lysine-63-linked ubiquitination and induces ER stress and cell proliferation.Toxicological research · 2025Article
- Lysine-63-linked polyubiquitination: a principal target of cadmium carcinogenesis.Toxicological research · 2024Review
- Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.Scientific reports · 2024Article
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cardiac physiology and metabolic gene expression during late organogenesis among F. heteroclitus embryo families from crosses between pollution-sensitive and -resistant parents.BMC ecology and evolution · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Signaling, proliferation, and inflammation are dependent on K63-linked ubiquitination-conjugation of a chain of ubiquitin molecules linked via lysine 63. However, very little information is currently available about how K63-linked ubiquitination is subverted in cancer. The present study provides, for the first time, evidence that cadmium (Cd), a widespread environmental carcinogen, is a potent activator of K63-linked ubiquitination, independently of oxidative damage, activation of ubiquitin ligase, or proteasome impairment. We show that Cd induces the formation of protein aggregates that sequester and inactivate cylindromatosis (CYLD) and selective autophagy, two tumor suppressors that deubiquitinate and degrade K63-ubiquitinated proteins, respectively. The aggregates are constituted of substrates of selective autophagy-SQSTM1, K63-ubiquitinated proteins, and mitochondria. These protein aggregates also cluster double-membrane remnants, which suggests an impairment in autophagosome maturation. However, failure to eliminate these selective cargos is not due to alterations in the general autophagy process, as degradation of long-lived proteins occurs normally. We propose that the simultaneous disruption of CYLD and selective autophagy by Cd feeds a vicious cycle that further amplifies K63-linked ubiquitination and downstream activation of the NF-κB pathway, processes that support cancer progression. These novel findings link together impairment of selective autophagy, K63-linked ubiquitination, and carcinogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.