A Role for Sam68 in Cell Cycle Progression Antagonized by a Spliced Variant within the KH Domain
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Sam68 is the main tyrosine-phosphorylated and Src-associated protein in mitotic cells. Sam68 exhibits a conserved functional KH (hnRNPK homology) RNA binding domain and binds single strand nucleic acids. Tyrosine phosphorylation mediates the interaction of Sam68 with many SH3- and SH2-containing proteins and negatively regulates its nucleic acid binding properties. But the function and the impact of Sam68 on cell signaling and cell proliferation remains elusive. We report here the identification of a natural isoform of Sam68 with a deletion within the KH domain. This isoform, called Sam68DeltaKH, is specifically expressed at growth arrest upon confluency in normal cells. In cells that do not enter quiescence at confluency such as Src-transformed cells, no recruitment of Sam68DeltaKH is observed. Transfected Sam68DeltaKH inhibits serum-induced DNA synthesis and cyclin D1 expression. Sam68 overcomes these effects, suggesting that isoforms of Sam68 are involved, through KH domain signaling, in cell proliferation, and more precisely in G1/S transition.
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Several noteworthy interactions include KHDRBS1, EGLN2, and BRI3BP.
“Several noteworthy interactions include a regulator of cell cycle progression, KHDRBS1 (ref. 72), the oxygen sensor, EGLN2 (ref. 73), and a stabilizer of p53, BRI3BP74”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [72]
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Retracted
- Authors
- Barlat, I., Maurier, F., Duchesne, M., Guitard, E., Tocque, B., & Schweighoffer, F.
- Corresponding author
- Schweighoffer, Fabien
- ORCID
- Maurier, Florence
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-02
- Volume
- 272
- Issue
- 6
- Pages
- 3129-3132
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2026506733
- Cited by
- 111
- References
- 22
- Citations by year
- 2024: 4 · 2023: 2 · 2021: 12 · 2019: 2 · 2018: 1 · 2016: 4 · 2015: 3 · 2013: 5 · 2012: 2
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Sam68, KH domain, alternative splicing, protein isoforms, cell cycle progression, G1/S transition, cyclin D1, tyrosine phosphorylation, RNA binding, cell proliferation, quiescence, confluency, DNA synthesis
- MeSH terms
- Cell Cycle, DNA-Binding Proteins, Humans, Phosphoproteins, Phosphorylation, Structure-Activity Relationship, Transfection, Tyrosine, Polymerase Chain Reaction, S Phase, RNA-Binding Proteins, Adaptor Proteins, Signal Transducing
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