Table 1.

Jumonji C (JmjC) histone demethylases play a role in inducing and suppressing cellular senescence.

JmjC Histone Demethylase	Target(s)	Implications in Senescence	Role in Suppressing Senescence to Promote Tumorigenesis
KDM6B	H3K27me3/2 H3K9me2/1 H4K20me1	Overexpression increases SASP gene expression [27]; promotes SAHF formation through pRb [28]; regulation of p53 [29]	Overexpressed in glioma cells to promote SASP expression [27]
KDM5B	H3K4me3/2	Silences E2F target genes [30,31]; knockdown increases H3K4 methylation at the CDKN2A locus [30]
KDM5A	H3K4me3/2	Knockdown or depletion induces senescence by increasing p21, p27, p16 [32,33]	Expression is required in pRb-defective cancer [34]
KDM4A	H3K36me3/2 H3K9me3/2	Downregulation activates the p53 pathway and induces PML body accumulation [35]	Cooperates with RAS to promote transformation [35]; affects the SASP [36]
KDM4B	H3K36me3/2 H3K9me3/2	No direct evidence; p53-responsive [37,38]; important for DSB repair [38,39]
KDM2B	H3K36me2/1 H3K4me3 H3K79me3/2	Demethylates CDKN2A [40] and CDKN2B loci [41]	Cooperates with KRAS to promote pancreatic cancer [42]; immortalizes MEFs [24,40]

SAHF: senescence-associated heterochromatin foci; SASP: senescence-associated secretory phenotype; pRB: retinoblastoma protein; DSB: double-stranded break.