ArticleThe Journal of clinical investigation2010
E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 31 citations in OpenAlex.
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- Vitamin B5 is a context-dependent dietary regulator of nociception.G3 (Bethesda, Md.) · 2024Article
- Ancient eukaryotic protein interactions illuminate modern genetic traits and disorders.bioRxiv : the preprint server for biology · 2024Article
- Neuroimmunomodulatory properties of polysialic acid.Glycoconjugate journal · 2023Review
- Computational analysis of prodomain cysteines in human TGF-β proteins reveals frequent loss of disulfide-dependent regulation in tumors.G3 (Bethesda, Md.) · 2022Article
- Clptm1 Limits Forward Trafficking of GABANeuron · 2018Article
- Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway.Nature communications · 2018Article
- Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins.Cold Spring Harbor perspectives in biology · 2016Review
- Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability.Nature communications · 2016Article
- Article
- Dendritic cell-derived thrombospondin-1 is critical for the generation of the ocular surface Th17 response to desiccating stress.Journal of leukocyte biology · 2013Article
- E-selectin ligand 1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Waking up HSCs: a new role for E-selectin.Nature medicine · 2012Article
- Haploinsufficiency of E-selectin ligand-1 is associated with reduced atherosclerotic plaque macrophage content while complete deficiency leads to early embryonic lethality in mice.Atherosclerosis · 2012Article
- Review
- Article
- Genetic regulation of the growth plate.Frontiers in endocrinology · 2011Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-beta signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-beta signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-beta is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand-1 (ESL-1), acts as a negative regulator of TGF-beta production by binding TGF-beta precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-beta by a furin-like protease, leading to reduced secretion of mature TGF-beta by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-beta/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-beta/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-beta during skeletal development and homeostasis.
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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.