ArticleCell death & disease2024
The NTE domain of PTENα/β promotes cancer progression by interacting with WDR5 via its SSSRRSS motif.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Structural insights into the MLH1-FAN1 interaction reveal an uncharacterized binding interface on MLH1.Nature communications · 2026Article
- Structural characterization of endogenous microprotein EMBOW reveals an alternative MRT motif for WDR5-interacting site recognition.The FEBS journal · 2026Article
- Article
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Crystal structures of Kif2A complexed with WDR5 reveal the structural plasticity of WIN-S7 sites.Acta biochimica et biophysica Sinica · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.
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