ArticleThe Biochemical journal2012
Selective STAT3-α or -β expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Palmitoylation-mediated regulation of KAT2A promotes lung metastasis in breast cancer.Nature cell biology · 2026Article
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs.Journal of cellular and molecular medicine · 2026Article
- STAT3 isoform dynamics reveal robust splice ratio maintenance across cytokine-activated human immune cells.Frontiers in immunology · 2026Article
- A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia.Cell death & disease · 2024Article
- Targeting STAT3 Enzyme for Cancer Treatment.Mini reviews in medicinal chemistry · 2024Review
- Structural determinants of mitochondrial STAT3 targeting and function.Mitochondrial communications · 2024Article
- RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.iScience · 2023Article
- Article
- Meprin β expression modulates the interleukin-6 mediated JAK2-STAT3 signaling pathway in ischemia/reperfusion-induced kidney injury.Physiological reports · 2022Article
- Characterization of plasma circulating small extracellular vesicles in patients with metastatic solid tumors and newly diagnosed brain metastasis.Oncoimmunology · 2022Article
- STAT3 phosphorylation in central leptin resistance.Nutrition & metabolism · 2021Review
- Article
- Review
- Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells-Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy.International journal of molecular sciences · 2020Article
- Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.Cells · 2020Review
- Master and servant: LINC00152 - a STAT3-induced long noncoding RNA regulates STAT3 in a positive feedback in human multiple myeloma.BMC medical genomics · 2020Article
- STAT3β is a tumor suppressor in acute myeloid leukemia.Blood advances · 2019Article
- PCBP1 inhibits the expression of oncogenic STAT3 isoform by targeting alternative splicing of STAT3 exon 23.International journal of biological sciences · 2019Article
- Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation of STAT3 (signal transducer and activator of transcription 3) is critical for its nuclear import and transcriptional activity. Although a shorter STAT3β spliceform was initially described as a negative regulator of STAT3α, gene knockout studies have revealed that both forms play critical roles. We have expressed STAT3α and STAT3β at comparable levels to facilitate a direct comparison of their functional effects, and have shown their different cytokine-stimulated kinetics of phosphorylation and nuclear translocation. Notably, the sustained nuclear translocation and phosphorylation of STAT3β following cytokine exposure contrasted with a transient nuclear translocation and phosphorylation of STAT3α. Importantly, co-expression of the spliceforms revealed that STAT3β enhanced and prolonged the phosphorylation and nuclear retention of STAT3α, but a STAT3β R609L mutant, with a disrupted SH2 (Src homology 2) domain, was not tyrosine phosphorylated following cytokine stimulation and could not cross-regulate STAT3α. The physiological importance of prolonged phosphorylation and nuclear retention was indicated by transcriptome profiling of STAT3(-/-) cells expressing either STAT3α or STAT3β, revealing the complexity of genes that are up- and down-regulated by the STAT3 spliceforms, including a distinct set of STAT3β-specific genes regulated under basal conditions and after cytokine stimulation. These results highlight STAT3β as a significant transcriptional regulator in its own right, with additional actions to cross-regulate STAT3α phosphorylation and nuclear retention after cytokine stimulation.
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