ArticleThe Journal of biological chemistry2016
Activated α2-Macroglobulin Regulates Transcriptional Activation of c-MYC Target Genes through Cell Surface GRP78 Protein.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Phosphosite-centric regulatory network of ATAD2 and its involvement in transcriptional networks.Molecular genetics and genomics : MGG · 2026Article
- Intracellular Signaling Regulated by Activated αInternational journal of molecular sciences · 2026Review
- Review
- Inhibition of cell surface GRP78 and activated α2M interaction attenuates kidney fibrosis.JCI insight · 2025Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Glucose-Regulated Protein 78, via Releasing β-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization.The American journal of pathology · 2024Article
- GRP78 inhibitor YUM70 upregulates 4E-BP1 and suppresses c-MYC expression and viability of oncogenic c-MYC tumors.Neoplasia (New York, N.Y.) · 2024Article
- COVID-19, Obesity, and GRP78: Unraveling the Pathological Link.Journal of obesity & metabolic syndrome · 2023Review
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway.Acta pharmaceutica Sinica. B · 2022Article
- GRP78, a Novel Host Factor for SARS-CoV-2: The Emerging Roles in COVID-19 Related to Metabolic Risk Factors.Biomedicines · 2022Review
- Review
- A2M is a potential core gene in intrahepatic cholangiocarcinoma.BMC cancer · 2022Article
- Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease.Biomedicines · 2021Article
- ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport.Cellular and molecular life sciences : CMLS · 2021Article
- CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia.Stem cell research & therapy · 2021Article
- GALNT6 promotes breast cancer metastasis by increasing mucin-type O-glycosylation of α2M.Aging · 2020Article
- Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling.The Journal of biological chemistry · 2019Article
- Molecular form and concentration of serum αScientific reports · 2019Article
- The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer.Cell death & disease · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated α2-macroglobulin (α2M*) signals predominantly through cell surface GRP78 (CS-GRP78) to promote proliferation and survival of cancer cells; however, the molecular mechanism remains obscure. c-MYC is an essential transcriptional regulator that controls cell proliferation. We hypothesize that α2M*/CS-GRP78-evoked key signaling events are required for transcriptional activation of c-MYC target genes. Activation of CS-GRP78 by α2M* requires ligation of the GRP78 primary amino acid sequence (Leu(98)-Leu(115)). After stimulation with α2M*, CS-GRP78 signaling activates 3-phosphoinositide-dependent protein kinase-1 (PDK1) to induce phosphorylation of PLK1, which in turn induces c-MYC transcription. We demonstrate that PLK1 binds directly to c-MYC and promotes its transcriptional activity by phosphorylating Ser(62) Moreover, activated c-MYC is recruited to the E-boxes of target genes FOSL1 and ID2 by phosphorylating histone H3 at Ser(10) In addition, targeting the carboxyl-terminal domain of CS-GRP78 with a mAb suppresses transcriptional activation of c-MYC target genes and impairs cell proliferation. This work demonstrates that α2M*/CS-GRP78 acts as an upstream regulator of the PDK1/PLK1 signaling axis to modulate c-MYC transcription and its target genes, suggesting a therapeutic strategy for targeting c-MYC-associated malignant progression.
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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.