ArticlePloS one2014
NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Linking shox/shox2 deficiency with fgfr3 gain-of-function and natriuretic peptides.Frontiers in endocrinology · 2026Article
- Genetic Heterogeneity Underlying Familial Short Stature.Diagnostics (Basel, Switzerland) · 2025Article
- A missense variant in the SOX5 gene (c.221C > T) is associated with intellectual disability.Orphanet journal of rare diseases · 2025Article
- Integrated transcriptomic analysis of human induced pluripotent stem cell-derived osteogenic differentiation reveals a regulatory role of KLF16.bioRxiv : the preprint server for biology · 2025Article
- Article
- Growth plate gene involment and isolated short stature.Endocrine · 2021Review
- Identification and Tissue-Specific Characterization of Novel SHOX-Regulated Genes in Zebrafish Highlights SOX Family Members Among Other Genes.Frontiers in genetics · 2021Article
- Detection of SHOX2 DNA methylation by methylation-specific PCR in non-small cell lung cancer.Translational cancer research · 2020Article
- Signaling pathways and clinical application of RASSF1A and SHOX2 in lung cancer.Journal of cancer research and clinical oncology · 2020Review
- The Short-Stature Homeobox-Containing Gene (Frontiers in endocrinology · 2017Article
- A Track Record on SHOX: From Basic Research to Complex Models and Therapy.Endocrine reviews · 2016Review
- SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature.Molecular syndromology · 2016Review
- Diagnosis of Lung Cancer by SHOX2 Gene Methylation Assay.Molecular diagnosis & therapy · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1) the natriuretic peptide precursor B gene (NPPB) involved in the endochondral ossification signalling and directly activated by SHOX; and 2) Aggrecan (ACAN), a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9) via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.
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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.