ArticleCell cycle (Georgetown, Tex.)2014
The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
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- Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells.Molecular carcinogenesis · 2023Article
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- Potassium Effects on NCC Are Attenuated during Inhibition of Cullin E3-Ubiquitin Ligases.Cells · 2021Article
- Targeting PP2A inhibits the growth of triple-negative breast cancer cells.Cell cycle (Georgetown, Tex.) · 2020Article
- Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats.Toxins · 2019Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Article
- Anticancer activity of NOB1-targeted shRNA combination with TRAIL in epithelial ovarian cancer cells.International journal of clinical and experimental pathology · 2015Article
- A dynamic interface between ubiquitylation and cAMP signaling.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase that regulates a number of cell signaling pathways. PP2A activity is controlled partially through protein degradation; however, the underlying mechanism is not fully understood. Here we show that PP2A/C, a catalytic subunit of PP2A, is degraded by the Cullin3 (Cul3) ligase-mediated ubiquitin-proteasome pathway. In response to death receptor signaling by tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL), PP2A/C, caspase-8 and Cul3, a subunit of the cullin family of E3 ligases, are recruited into the death-inducing signaling complex (DISC) where the Cul3 ligase targets PP2A/C for ubiquitination and subsequent degradation. Functionally, knockdown of PP2A/C expression by siRNA or pharmacological inhibition of PP2A activity increases TRAIL-induced apoptosis. In cancer cells that have developed acquired TRAIL resistance, PP2A phosphatase activity is increased, and PP2A/C protein is resistant to TRAIL-induced degradation. Thus, this work identifies a new mechanism by which PP2A/C is regulated by Cul3 ligase-mediated degradation in response to death receptor signaling and suggests that inhibition of PP2A/C degradation may contribute to resistance of cancer cells to death receptor-induced apoptosis.
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