ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Signaling mechanism of tumor cell-induced up-regulation of E3 ubiquitin ligase UBR2.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Cancer cachexia: A tumor-driven disorder of whole-body homeostasis.Cancer cell · 2026Review
- Genome-wide analysis of somatic noncoding mutation patterns and mitochondrial heteroplasmic shift in type B1 and B2 thymomas.The Journal of pathology · 2026Article
- TAK-242 inhibits toll-like receptor-4 signaling and attenuates cancer-associated muscle atrophy via the p38-C/EBPβ pathway.Journal of molecular histology · 2025Article
- An alternative pocket for binding the N-degrons by the UBR1 and UBR2 ubiquitin E3 ligases.Protein science : a publication of the Protein Society · 2025Article
- SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response.Cell reports · 2025Article
- Decoupling FcRn and tumor contributions to elevated immune checkpoint inhibitor clearance in cancer cachexia.Pharmacological research · 2024Article
- Research progress on exosomal proteins as diagnostic markers of gastric cancer (review article).Clinical and experimental medicine · 2023Review
- Interruption of the long non-coding RNA HOTAIR signaling axis ameliorates chemotherapy-induced cachexia in bladder cancer.Journal of biomedical science · 2022Article
- UBR2 targets myosin heavy chain IIb and IIx for degradation: Molecular mechanism essential for cancer-induced muscle wasting.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90.Cells · 2022Article
- Tumor cell anabolism and host tissue catabolism-energetic inefficiency during cancer cachexia.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Ameliorating cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90 with omeprazole.Journal of cachexia, sarcopenia and muscle · 2022Article
- Identification and validation of a five apoptosis-related genes signature for prediction of disease-free survival for testicular germ cell tumors.Translational andrology and urology · 2021Article
- Cancer-Induced Muscle Wasting Requires p38β MAPK Activation of p300.Cancer research · 2021Article
- Weight Loss in Cancer Patients Correlates With p38β MAPK Activation in Skeletal Muscle.Frontiers in cell and developmental biology · 2021Article
- The E3 ligase UBR2 regulates cell death under caspase deficiency via Erk/MAPK pathway.Cell death & disease · 2020Article
- Downregulation of the Arg/N-degron Pathway Sensitizes Cancer Cells to Chemotherapy In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Effects of conditioned media from murine lung cancer cells and human tumor cells on cultured myotubes.American journal of physiology. Endocrinology and metabolism · 2020Article
- Cancer Takes a Toll on Skeletal Muscle by Releasing Heat Shock Proteins-An Emerging Mechanism of Cancer-Induced Cachexia.Cancers · 2019Review
- A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice.Cell reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The N-end rule pathway contributes significantly to accelerated muscle proteolysis mediated by the ubiquitin-proteasome pathway in various catabolic conditions. UBR2 (aka E3α-II) is the only known E3 ubiquitin ligase of the N-end rule pathway that is up-regulated by cachectic stimuli including proinflammatory cytokines and tumors. However, the signaling mechanism through which UBR2 is up-regulated remains undetermined. Here we identify a signaling pathway that mediates tumor cell-induced up-regulation of UBR2. UBR2 expression in C2C12 myotubes was up-regulated by conditioned medium from Lewis lung carcinoma cells or C26 colon adenocarcinoma cells, which was blocked by a pharmacological inhibitor of p38α/β mitogen-activated protein kinase (MAPK), SB202190. Similarly, SB202190 administration (i.p.) abolished UBR2 up-regulation in the tibialis anterior of LLC tumor-bearing mice. Genetic gain and loss of function assays in C2C12 myotubes indicated that tumor-induced activation of the p38β isoform is sufficient and necessary for UBR2 up-regulation. In addition, UBR2 up-regulation required p38β-mediated phosphorylation of CCAAT/enhancer binding protein (C/EBP)-β Thr-188, which was critical to C/EBPβ binding to the UBR2 promoter. Furthermore, luciferase reporter assay revealed that the C/EBPβ binding motif in the UBR2 promoter is a functional C/EBPβ-responsive cis-element that enhances the promoter activity on activation by p38β. Finally, genetic ablation of C/EBPβ blocked UBR2 up-regulation in LLC tumor-bearing mice. These results suggest that UBR2 up-regulation in cachectic muscle is mediated by the p38β-C/EBPβ signaling pathway responsible for the bulk of tumor-induced muscle proteolysis.
Indexed as
Identifiers
What OpenQuestion holds
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.