ArticleJournal of cellular physiology2014
Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells.
Article in Journal of cellular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 58 citations in OpenAlex.
- Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy.Physiology (Bethesda, Md.) · 2027Review
- Hepatitis C Virus NS5A Inhibits YAP1-HSC70 Interaction, Thereby Preventing YAP1 Degradation Via Chaperone-Mediated Autophagy.The Kobe journal of medical sciences · 2025Article
- Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Ex.50.T aptamer impairs tumor-stroma cross-talk in breast cancer by targeting gremlin-1.Cell death discovery · 2025Article
- Multiple regulatory mechanisms, functions and therapeutic potential of chaperone-mediated autophagy.Theranostics · 2025Review
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis.Molecular cancer · 2024Article
- The endolysosomal system in conventional and unconventional protein secretion.The Journal of cell biology · 2024Review
- The Role of Chaperone-Mediated Autophagy in Tissue Homeostasis and Disease Pathogenesis.Biomedicines · 2024Review
- The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.Current pharmaceutical design · 2024Review
- LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.Autophagy · 2023Review
- The Complex Role of Chaperone-Mediated Autophagy in Cancer Diseases.Biomedicines · 2023Review
- Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression.Frontiers in cell and developmental biology · 2022Article
- A perspective on the role of autophagy in cancer.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Role of chaperone-mediated autophagy in the pathophysiology including pulmonary disorders.Inflammation and regeneration · 2021Review
- Inhibition of chaperone‑mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer.Molecular medicine reports · 2021Article
- miR-34c-3p targets CDK1 a synthetic lethality partner of KRAS in non-small cell lung cancer.Cancer gene therapy · 2021Article
- Discovery of LAMP-2A as potential biomarkers for glioblastoma development by modulating apoptosis through N-CoR degradation.Cell communication and signaling : CCS · 2021Article
- Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70 kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms.
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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.