ArticleMolecular and cellular biology2014
Chromosome instability underlies hematopoietic stem cell dysfunction and lymphoid neoplasia associated with impaired Fbw7-mediated cyclin E regulation.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- FBXW7 in breast cancer: mechanism of action and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2023Review
- Ubiquitin E3 ligases in cancer: somatic mutation and amplification.BMB reports · 2023Review
- Comprehensive characterization of FBXW7 mutational and clinicopathological profiles in human colorectal cancers.Frontiers in oncology · 2023Article
- FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies.Frontiers in oncology · 2022Review
- miR-212/132-Enriched Extracellular Vesicles Promote Differentiation of Induced Pluripotent Stem Cells Into Pancreatic Beta Cells.Frontiers in cell and developmental biology · 2021Article
- Regulation of Normal and Malignant Hematopoiesis by FBOX Ubiquitin E3 Ligases.Trends in immunology · 2020Review
- Transformation of Hematopoietic Stem and Progenitor Cells by Leukemia Extracellular Vesicles: A Step Toward Leukemogenesis.Stem cell reviews and reports · 2020Review
- Loss of Fbxw7 triggers mammary tumorigenesis associated with E2F/c-Myc activation and Trp53 mutation.Neoplasia (New York, N.Y.) · 2020Article
- Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective.Comprehensive Physiology · 2019Review
- Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia.Oncotarget · 2018Review
- The PP2A-B56 Phosphatase Opposes Cyclin E Autocatalytic Degradation via Site-Specific Dephosphorylation.Molecular and cellular biology · 2017Article
- The role of cullin4B in human cancers.Experimental hematology & oncology · 2017Review
- E2F-2 Promotes Nuclear Condensation and Enucleation of Terminally Differentiated Erythroblasts.Molecular and cellular biology · 2017Article
- Fbxw7 Deletion Accelerates KrasNeoplasia (New York, N.Y.) · 2016Article
- Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis.Seminars in cancer biology · 2016Review
- Emerging roles for the FBXW7 ubiquitin ligase in leukemia and beyond.Current opinion in cell biology · 2015Review
- The role of aberrant proteolysis in lymphomagenesis.Current opinion in hematology · 2015Review
- Pim kinases in hematological malignancies: where are we now and where are we going?Journal of hematology & oncology · 2014Review
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The Fbw7 ubiquitin ligase critically regulates hematopoietic stem cell (HSC) function, though the precise contribution of individual substrate ubiquitination pathways to HSC homeostasis is unknown. In the work reported here, we used a mouse model in which we introduced two knock-in mutations (T74A and T393A [changes of T to A at positions 74 and 393]) to disrupt Fbw7-dependent regulation of cyclin E, its prototypic substrate, and to examine the consequences of cyclin E dysregulation for HSC function. Serial transplantation revealed that cyclin E(T74A T393A) HSCs self-renewed normally; however, we identified defects in their multilineage reconstituting capacity. By inducing hematologic stress, we exposed an impaired self-renewal phenotype in cyclin E knock-in HSCs that was associated with defective cell cycle exit and the emergence of chromosome instability (CIN). Importantly, p53 deletion induced both defects in self-renewal and multilineage reconstitution in cyclin E knock-in HSCs with serial transplantation and CIN in hematopoietic stem and progenitor cells. Moreover, CIN was a feature of fatal T-cell malignancies that ultimately developed in recipients of cyclin E(T74A T393A); p53-null HSCs. Together, our findings demonstrate the importance of Fbw7-dependent cyclin E control to the hematopoietic system and highlight CIN as a characteristic feature of HSC dysfunction and malignancy induced by deregulated cyclin E.
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Registered trials
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