ArticleMolecular cancer research : MCR2012
The proteasome activator PA200 regulates tumor cell responsiveness to glutamine and resistance to ionizing radiation.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.International journal of molecular sciences · 2024Review
- The proteasome regulator PSME4 modulates proteasome activity and antigen diversity to abrogate antitumor immunity in NSCLC.Nature cancer · 2023Article
- Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer.Cancer research · 2023Article
- Review of possible mechanisms of radiotherapy resistance in cervical cancer.Frontiers in oncology · 2023Review
- The Proteasome Activator PA200/PSME4: An Emerging New Player in Health and Disease.Biomolecules · 2022Review
- Histone degradation by the proteasome regulates chromatin and cellular plasticity.The FEBS journal · 2022Review
- Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance.Frontiers in oncology · 2022Review
- Immune-related gene expression signatures in colorectal cancer.Oncology letters · 2021Article
- The Expression Patterns and Prognostic Value of the Proteasome Activator Subunit Gene Family in Gastric Cancer Based on Integrated Analysis.Frontiers in cell and developmental biology · 2021Article
- Jab1 promotes gastric cancer tumorigenesis via non-ubiquitin proteasomal degradation of p14ARF.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- The proteasome activator PA200 regulates expression of genes involved in cell survival upon selective mitochondrial inhibition in neuroblastoma cells.Journal of cellular and molecular medicine · 2020Article
- Cellular Responses to Proteasome Inhibition: Molecular Mechanisms and Beyond.International journal of molecular sciences · 2019Review
- A Practical Review of Proteasome Pharmacology.Pharmacological reviews · 2019Review
- Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer.Frontiers in oncology · 2019Review
- Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.Frontiers in molecular biosciences · 2019Review
- Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.Oncotarget · 2018Article
- Inhibition of Proteasome Activity Induces Formation of Alternative Proteasome Complexes.The Journal of biological chemistry · 2016Article
- GWASdb v2: an update database for human genetic variants identified by genome-wide association studies.Nucleic acids research · 2016Article
- Article
- Proteasomes associated with the Blm10 activator protein antagonize mitochondrial fission through degradation of the fission protein Dnm1.The Journal of biological chemistry · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The cellular response to ionizing radiation (IR) involves a variety of mechanisms to repair damage and maintain cell survival. We previously reported that the proteasome activator PA200 promotes long-term cell survival after IR exposure. The molecular function of PA200 is to enhance proteasome-mediated cleavage after glutamate; however, it is not known how this molecular function promotes survival after IR exposure. Here, we report that upon IR exposure, cellular demand for exogenous glutamine is increased. Cells containing PA200 are capable of surviving this IR-induced glutamine demand, whereas PA200-deficient cells show impaired long-term survival. Additional glutamine supplementation reverses the radiosensitivity of PA200-knockdown cells suggesting impaired glutamine homeostasis in these cells. Indeed, PA200-knockdown cells are unable to maintain intracellular glutamine levels. Furthermore, when extracellular glutamine is limiting, cells that contain PA200 respond by slowing growth, but PA200-knockdown cells and cells in which post-glutamyl proteasome activity is inhibited are nonresponsive and continue rapid growth. This cellular unresponsiveness to nutrient depletion is also reflected at the level of the mTOR substrate ribosomal S6 kinase (S6K). Thus, inability to restrict growth causes PA200-deficient cells to continue growing and eventually die due to lack of available glutamine. Together, these data indicate an important role for PA200 and post-glutamyl proteasome activity in maintaining glutamine homeostasis, which appears to be especially important for long-term survival of tumor cells after radiation exposure.
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Registered trials
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.