ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018
Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Schlafen 5 is an intracellular immune checkpoint and controls IFN responses in pancreatic ductal adenocarcinoma.JCI insight · 2026Article
- Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes.Genome biology and evolution · 2025Article
- SLFN12 Expression Significantly Effects the Response to Chemotherapy Drugs in Triple-Negative Breast Cancer.Cancers · 2024Article
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- Vil-Cre specific Slfn3KO mice exhibit sex-specific differences in lung, stomach, cecum, kidney, and proximal colon differentiation markers and Slfn family members expression levels.Biochemistry and biophysics reports · 2023Article
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- Schlafen 12 Slows TNBC Tumor Growth, Induces Luminal Markers, and Predicts Favorable Survival.Cancers · 2023Article
- Article
- The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.JCI insight · 2022Article
- Schlafens Can Put Viruses to Sleep.Viruses · 2022Review
- Structural and biochemical characterization of human Schlafen 5.Nucleic acids research · 2022Article
- Review
- Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.Nature communications · 2021Article
- ZINC40099027 activates human focal adhesion kinase by accelerating the enzymatic activity of the FAK kinase domain.Pharmacology research & perspectives · 2021Article
- Article
- Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Article
- Microphysiological Engineering of Immune Responses in Intestinal Inflammation.Immune network · 2020Review
- Mechanistic insights into cancer cell killing through interaction of phosphodiesterase 3A and schlafen family member 12.The Journal of biological chemistry · 2020Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsHuman enterocytic differentiation is altered during development, fasting, adaptation, and bariatric surgery, but its intracellular control remains unclear. We hypothesized that Schlafen 12 (SLFN12) regulates enterocyte differentiation.
methodsWe used laser capture dissection of epithelium, qRT-PCR, and immunohistochemistry to evaluate SLFN12 expression in biopsies of control and fasting human duodenal mucosa, and viral overexpression and siRNA to trace the SLFN12 pathway in human Caco-2 and HIEC6 intestinal epithelial cells.
resultsFasting human duodenal mucosa expressed less SLFN12 mRNA and protein, accompanied by decreases in enterocytic markers like sucrase-isomaltase. SLFN12 overexpression increased Caco-2 sucrase-isomaltase promoter activity, mRNA, and protein independently of proliferation, and activated the SLFN12 putative promoter. SLFN12 coprecipitated Serpin B12 (SERPB12). An inactivating SLFN12 point mutation prevented both SERPB12 binding and sucrase-isomaltase induction. SERPB12 overexpression also induced sucrase-isomaltase, while reducing SERPB12 prevented the SLFN12 effect on sucrase-isomaltase. Sucrase-isomaltase induction by both SLFN12 and SERPB12 was attenuated by reducing UCHL5 or USP14, and blocked by reducing both. SERPB12 stimulated USP14 but not UCHL5 activity. SERPB12 coprecipitated USP14 but not UCHL5. Moreover, SLFN12 increased protein levels of the sucrase-isomaltase-promoter-binding transcription factor cdx2 without altering Cdx2 mRNA. This was prevented by reducing UCHL5 and USP14. We further validated this pathway in vitro and in vivo. SLFN12 or SERPB12 overexpression induced sucrase-isomaltase in human non-malignant HIEC-6 enterocytes.
conclusionsSLFN12 regulates human enterocytic differentiation by a pathway involving SERPB12, the deubiquitylases, and Cdx2. This pathway may be targeted to manipulate human enterocytic differentiation in mucosal atrophy, short gut or obesity.
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