ArticleOncogene2012
Syntenin-mediated regulation of Sox4 proteasomal degradation modulates transcriptional output.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Activation of human endogenous retroviruses by Sox proteins induces cell apoptosis via the caspase-3 pathway.Frontiers in microbiology · 2025Article
- Choline Regulates SOX4 through miR-129-5p and Modifies H3K27me3 in the Developing Cortex.Nutrients · 2023Article
- The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression.International journal of molecular sciences · 2023Review
- Spin column-based peptide fractionation alternatives for streamlined tandem mass tag (SL-TMT) sample processing.Journal of proteomics · 2023Article
- Biological Role and Aberrant Overexpression of Syntenin-1 in Cancer: Potential Role as a Biomarker and Therapeutic Target.Biomedicines · 2023Review
- Article
- Syntenin-knock out reduces exosome turnover and viral transduction.Scientific reports · 2021Article
- Article
- Long non-coding RNA TGLC15 advances hepatocellular carcinoma by stabilizing Sox4.Journal of clinical laboratory analysis · 2020Article
- SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis.Nucleic acids research · 2018Article
- Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis.Oncotarget · 2016Article
- SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation.Cancer research · 2016Article
- MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma.Oncotarget · 2016Article
- Regulation of Proteasomal Degradation by Modulating Proteasomal Initiation Regions.ACS chemical biology · 2015Article
- Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2.Molecular & cellular proteomics : MCP · 2015Article
- Hepatitis B virus replication and sex-determining region Y box 4 production are tightly controlled by a novel positive feedback mechanism.Scientific reports · 2015Article
- Targeting tumor invasion: the roles of MDA-9/Syntenin.Expert opinion on therapeutic targets · 2015Review
- Pleiotropic function of SRY-related HMG box transcription factor 4 in regulation of tumorigenesis.Cellular and molecular life sciences : CMLS · 2013Review
- The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe?Oncogene · 2013Review
- A functional CFTR assay using primary cystic fibrosis intestinal organoids.Nature medicine · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor Sox4 is aberrantly expressed in many human tumors and can modulate tumorigenesis and metastases of murine tumors in vivo. However, mechanisms that control Sox4 function remain poorly defined. It has recently been observed that DNA damage increases Sox4 protein expression independently of Sox4 mRNA levels, suggesting an as yet undefined post-transcriptional mechanism regulating Sox4 expression and functionality. Here, we show that Sox4 protein is rapidly degraded by the proteasome as indicated by pharmacological inhibition with Mg132 and epoxymycin. Sox4 half-life was found to be less than 1 h as evident by inhibition of protein synthesis using cycloheximide. Ectopic expression of Sox4 deletion mutants revealed that the C-terminal 33 residues of Sox4 were critical in modulating its degradation in a polyubiquitin-independent manner. Syntenin, a Sox4 binding partner, associates with this domain and was found to stabilize Sox4 expression. Syntenin-induced stabilization of Sox4 correlated with Sox4-syntenin relocalization to the nucleus, where both proteins accumulate. Syntenin overexpression or knockdown in human tumor cell lines was found to reciprocally modulate Sox4 protein expression and transcriptional activity implicating its role as a regulator of Sox4. Taken together, our data demonstrate that the Sox4 C-terminal domain regulates polyubiquitin-independent proteasomal degradation of Sox4 that can be modulated by interaction with syntenin. As aberrant Sox4 expression has been found associated with many human cancers, modulation of Sox4 proteasomal degradation may impact oncogenesis and metastatic properties of tumors.
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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.