ArticleThe Journal of cell biology2007
The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x.
Article in The Journal of cell biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.
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Who cites it
196 citing papers in PubMed, 336 citations in OpenAlex.
- Citron kinase activity controls alternative splicing events that drive prostate cancer growth.Science advances · 2026Article
- CircLAMA5 traps Sam68 in the cytoplasm to regulate alternative splicing and drive sunitinib resistance in ccRCC.Oncogene · 2026Article
- Assessment of Aggregation- and Condensation-Prone Regions of Proteins Involved in Neurodegenerative, Neurological and Mental-State Diseases.Biomolecules · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- YTHDC1 functions as a molecular chaperone to suppress ALS-linked hnRNPA1 mutants from aggregation.Nature communications · 2026Article
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- SAM68 is a multifunctional post-transcriptional regulator of cardiomyocyte differentiation.Nucleic acids research · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Diverse roles of quaking in endothelial cell biology.Angiogenesis · 2025Review
- An intron-based timer for circadian rhythms.bioRxiv : the preprint server for biology · 2025Article
- A variant form of receptor activator of nuclear factor-κB functions as an osteoprotegerin mimic in bone and cardiac development.Scientific reports · 2025Article
- Repurposing alternative splicing events as potential targets for the design of diagnostic and therapeutic tools in PCa.Frontiers in oncology · 2025Review
- Role of Sam68 in different types of cancer (Review).International journal of molecular medicine · 2025Review
- Decellularized adipose-derived matrix from Superficial layers of abdominal adipose tissue exhibits superior capacity of adipogenesis compared to deep layers.Materials today. Bio · 2024Article
- Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging.Ageing research reviews · 2024Review
- The Regulatory Network of hnRNPs Underlying RegulatingBiomolecules · 2024Review
- Differential expression of paralog RNA binding proteins establishes a dynamic splicing program required for normal cerebral cortex development.Nucleic acids research · 2024Article
- An in vitro CRISPR screen of cell-free DNA identifies apoptosis as the primary mediator of cell-free DNA release.Communications biology · 2024Article
- Unearthing the role of septins in viral infections.Bioscience reports · 2024Review
- SAM68 directs STING signaling to apoptosis in macrophages.Communications biology · 2024Article
136 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.
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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.