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The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Biological validation that SF3b is a target of the antitumor macrolide pladienolide

Open access
Yokoi, Akira, Kotake, Yoshihiko, Takahashi, Kentaro, Kadowaki, Tadashi, Matsumoto, Yoshiko, Minoshima, Yukinori, Sugi, Naoko H., Sagane, Koji, Hamaguchi, Makoto, Iwata, Masao, Mizui, Yoshiharu·2011·The FEBS Journal

Abstract

Pladienolide is a naturally occurring macrolide that binds to the SF3b complex to inhibit mRNA splicing. It has not been fully validated whether the splicing impairment is a relevant mechanism for the potent antitumor activity of pladienolide. We established pladienolide‐resistant clones from WiDr and DLD1 colorectal cancer cells that were insensitive to the inhibitory action of pladienolide on cell proliferation and splicing. An mRNA‐Seq differential analysis revealed that these two cell lines have an identical mutation at Arg1074 in the gene for SF3B1, which encodes a subunit of the SF3b complex. Reverse expression of the mutant protein transferred pladienolide resistance to WiDr cells. Furthermore, immunoprecipitation analysis using a radiolabeled probe showed that the mutation impaired the binding affinity of paldienolide to its target. These results clearly demonstrate that pladienolide exerts its potent activity by targeting SF3b and also suggest that inhibition of SF3b is a promising drug target for anticancer therapy. Structured digital abstract SF3B1physically interacts with SF3B2 and SF3B3 by anti bait coimmunoprecipitation (View interaction)

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Crossref · 10.1111/j.1742-4658.2011.08387.x

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Metadata

Authors
Yokoi, A., Kotake, Y., Takahashi, K., Kadowaki, T., Matsumoto, Y., Minoshima, Y., Sugi, N. H., Sagane, K., Hamaguchi, M., Iwata, M., & Mizui, Y.
Venue
The FEBS Journal
Publisher
Wiley
Published
2011-10-31
Volume
278
Issue
24
Pages
4870-4880
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
OpenAlex
W1553320576
Cited by
177
References
1
FWCI
2.94
Type
journal article
Language
en
Open access
bronze

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The paper
Yokoi, A., Kotake, Y., Takahashi, K., Kadowaki, T., Matsumoto, Y., Minoshima, Y., Sugi, N. H., Sagane, K., Hamaguchi, M., Iwata, M., & Mizui, Y. (2011). Biological validation that SF3b is a target of the antitumor macrolide pladienolide. The FEBS Journal. https://doi.org/10.1111/j.1742-4658.2011.08387.x

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