ArticleBlood2010
Ubiquitination and degradation of the thrombopoietin receptor c-Mpl.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 92 citations in OpenAlex.
- Personalized Management of Cytopenias in Chronic Liver Disease: From Pathophysiology to Treatment Strategies.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- Recombinant human thrombopoietin for chronic liver disease-associated thrombocytopenia with or without concomitant infections: a real-world retrospective study.Frontiers in pharmacology · 2026Article
- Review
- Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms.Blood advances · 2024Article
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- Sensitivity to targeted UBA1 inhibition in a myeloid cell line model of VEXAS syndrome.Blood advances · 2023Article
- Uncovering complex trait heritability hidden in the repeatome.Cell genomics · 2023Article
- Polymorphic short tandem repeats make widespread contributions to blood and serum traits.Cell genomics · 2023Article
- ANKRD26 is a new regulator of type I cytokine receptor signaling in normal and pathological hematopoiesis.Haematologica · 2023Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures.World journal of gastroenterology · 2022Review
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- New functions of C3G in platelet biology: Contribution to ischemia-induced angiogenesis, tumor metastasis and TPO clearance.Frontiers in cell and developmental biology · 2022Article
- Platelet proteome and function in X-linked thrombocytopenia with thalassemia andHaematologica · 2021Article
- MPL overexpression induces a high level of mutant-CALR/MPL complex: a novel mechanism of ruxolitinib resistance in myeloproliferative neoplasms with CALR mutations.International journal of hematology · 2021Article
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
- GPIbα is the driving force of hepatic thrombopoietin generation.Research and practice in thrombosis and haemostasis · 2021Article
- The Role of the Proteasome in Platelet Function.International journal of molecular sciences · 2021Review
- C-Cbl regulates c-MPL receptor trafficking and its internalization.Journal of cellular and molecular medicine · 2020Article
- It's reticulated: the liver at the heart of atherosclerosis.The Journal of endocrinology · 2018Review
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of growth factor and cytokine signaling is essential for maintaining physiologic numbers of circulating hematopoietic cells. Thrombopoietin (Tpo), acting through its receptor c-Mpl, is required for hematopoietic stem cell maintenance and megakaryopoiesis. Therefore, the negative regulation of Tpo signaling is critical in many aspects of hematopoiesis. In this study, we determine the mechanisms of c-Mpl degradation in the negative regulation of Tpo signaling. We found that, after Tpo stimulation, c-Mpl is degraded by both the lysosomal and proteasomal pathways and c-Mpl is rapidly ubiquitinated. Using site-directed mutagenesis, we were able to determine that c-Mpl is ubiquitinated on both of its intracellular lysine (K) residues (K(553) and K(573)). By mutating these residues to arginine, ubiquitination and degradation were significantly reduced and caused hyperproliferation in cell lines expressing these mutated receptors. Using short interfering RNA and dominant negative overexpression, we also found that c-Cbl, which is activated by Tpo, acts as an E3 ubiquitin ligase in the ubiquitination of c-Mpl. Our findings identify a previously unknown negative regulatory pathway for Tpo signaling that may significantly impact our understanding of the mechanisms affecting the growth and differentiation of hematopoietic stem cells and megakaryocytes.
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.