ArticleCancer research2015
Usp28 counteracts Fbw7 in intestinal homeostasis and cancer.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Pooled it
- Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance.Frontiers in immunology · 2026Review
- Cancer-associated USP28 missense mutations disrupt 53BP1 interaction and p53 stabilization.Nature communications · 2025Article
- Article
- USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer.Cell death & disease · 2025Article
- Review
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- The dimeric deubiquitinase USP28 integrates 53BP1 and MYC functions to limit DNA damage.Nucleic acids research · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.Frontiers in cell and developmental biology · 2024Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Article
- USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer.Cell death and differentiation · 2023Article
- The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells.The Journal of biological chemistry · 2023Article
- Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development.Experimental hematology & oncology · 2023Review
- Ubiquitin-specific protease 28 deubiquitinates TCF7L2 to govern the action of the Wnt signaling pathway in hepatic carcinoma.Cancer science · 2022Article
- The paradoxical roles of miR-4295 in human cancer: Implications in pathogenesis and personalized medicine.Genes & diseases · 2022Review
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation.Cell death & disease · 2022Review
- Fbw7 Inhibits the Progression of Activated B-Cell Like Diffuse Large B-Cell Lymphoma by Targeting the Positive Feedback Loop of the LDHA/lactate/miR-223 Axis.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The stability of several oncoproteins, including c-Myc, is regulated by ubiquitin-dependent degradation mediated by the SCF(Fbw7) ubiquitin ligase. This activity is antagonized by the deubiquitinase Usp28, which is highly expressed in murine and human intestinal cancers. Usp28 was previously shown to interact with its substrates via a "piggyback" interaction with Fbw7, which suggested that Fbw7 is required for Usp28 activity. Unexpectedly, we found that genetic deletion of Usp28 rescued the lethality of Fbw7-deficient primary fibroblasts. Moreover, Usp28 inactivation in the intestine (Usp28(ΔIEC)) ameliorated the hyperproliferation and the impaired goblet and Paneth cell differentiation observed in Fbw7(ΔIEC) mice. The aggressive intestinal tumor formation of APC(Min/+); Fbw7(ΔIEC) mice was restrained when Usp28 was inactivated concomitantly. In both fibroblasts and intestinal cells, Usp28 deficiency corrected the accumulation of SCF(Fbw7) substrate proteins, including NICD1, c-Jun, and c-Myc. These findings suggested that Usp28 function does not depend on the presence of Fbw7, but instead independently recognizes and deubiquitylates the same substrates as SCF(Fbw7). Fbw7 binds to a phosphorylated motif termed the phosphodegron and we found that Usp28 also interacted with this same motif, but only when it is unphosphorylated, offering a mechanistic explanation for identical substrate selection by Fbw7 and Usp28. Our results indicate an unusually direct antagonism between an E3 ligase and a deubiquitinase, Fbw7 and Usp28, in modulating intestinal homeostasis and cancer.
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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.