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SENESCENCE

A role for CUX1 in the regulation of p16 and senescence

Nature Aging volume 2, pages 100–101 (2022)Cite this article

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Vascular senescence has been implicated in atherosclerosis. By characterizing SNPs in the p16-encoding CDKN2A/B locus, a new study in Nature Aging identifies CUX1 as a binding protein of an atherosclerosis-associated functional SNP, which activates CDKN2A expression and senescence in endothelial cells, thus providing a mechanism of transcriptional senescence regulation.

Using a sequential approach recently developed by the authors6, functional SNP candidates were first determined from a library of SNPs in the CDKN2A/B locus as targets of allele-imbalanced binding proteins. Among the hits, they focused on the SNP rs1537371, which is strongly associated with atherosclerosis, and identified CUX1 from the nuclear extract of human arterial endothelial cells as having preferential binding to the risk over the non-risk allele (Fig. 1a).

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Fig. 1: Identification of functional SNPs and associated binding proteins reveals a role of CUX1 in endothelial cell senescence.

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  1. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK

    Adelyne Sue Li Chan & Masashi Narita

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  1. Adelyne Sue Li Chan
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  2. Masashi Narita
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Correspondence to Masashi Narita.

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The authors declare no competing interests.

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Chan, A.S.L., Narita, M. A role for CUX1 in the regulation of p16 and senescence. Nat Aging 2, 100–101 (2022). https://doi.org/10.1038/s43587-022-00173-4

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