Post-GWAS functional analysis identifies CUX1 as a regulator of p16^INK4a and cellular senescence.

ABSTRACT: Accumulation of senescent cells with age is an important driver of aging and age-related diseases. However, the mechanisms and signaling pathways that regulate senescence remain elusive. In this report, we performed post-genome-wide association studies (GWAS) functional studies on the CDKN2A/B locus, a locus known to be associated with multiple age-related diseases and overall human lifespan. We demonstrate that transcription factor CUX1 (Cut-Like Homeobox 1) specifically binds to an atherosclerosis-associated functional single-nucleotide polymorphism (fSNP) (rs1537371) within the locus and regulates the CDKN2A/B-encoded proteins p14^ARF, p15^INK4b and p16^INK4a and the antisense noncoding RNA in the CDK4 (INK4) locus (ANRIL) in endothelial cells (ECs). Endoth

SUBMITTER: Jiang D 

PROVIDER: S-EPMC10154215 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature