Table 1. Novel genes identified in reverse-genetics senescence bypass screens.

The table shows the diversity of genes which either promote senescence or its bypass as identified in cellular screens for senescence bypass. Genes well known to be important in cellular senescence such as p53, p21 and PAI-1 are not included here. ^aOther genes identified in this screen: BNIP3L, BIN1, HSPA9, IL1R1, PEA15, RAP1GAP, DMTF1, FOXA1, IRF1, MEN1, HIRA, SMARCB1, FBXO31, NF2 [25]. ^bAdditional genes identified in this screen: RPS6KA6, HTATIP, HDAC4, SAH3, CCT2 [24].

Gene	Promotion or inhibition of senescence	Potential senescence-associated pathway/mechanism of action	Biological Function	Refe-rence	Cell type
BCL6	inhibition	Induces cyclin D1 expression and renders cells unresponsive to antiproliferative signals from the p19(ARF)-p53 pathway	Transcription factor	[29]	MEFs, human B cells
Bub1	inhibition	Bub1 RNAi induces senescence. Bub1 expression does not extend lifespan	Mitotic checkpoint Ser/Thr kinase	[25a, 28, 42]	Primary MEFs
Csn2	promotion	Inactivation inhibits p53 transcriptional activity and confers resistance to both p53- and p16INK4a-induced proliferation arrest	Component of the Cop9 signalosome	[28]	Primary MEFs
Brf1	promotion	Inhibition of p53 transcription and reduction p16ink4a-induced arrest	Subunit of the RNA polymerase II complex	[28]	Primary MEFs
Aldose Reductase	promotion	Inhibition of p53 transcription and reduction p16ink4a-induced arrest	Metabolic enzyme - glucose metabolism	[28]	Primary MEFs
Tid1	induction	Tid1 is a repressor of NF-κB signaling	DNA-J like protein which functions as a co-chaperone	[43]	Rat embryo fibroblasts
hDRIL1	inhibition	Renders primary MEFs unresponsive to RAS(V12)-induced anti-proliferative signaling by p19(ARF)/p53/p21(CIP1), as well as by p16(INK4a) Binds E2F1 and induces Cyclin E1	Transcription factor	[32]	MEFs RASV12 induced senescence
CBX7	inhibition	Controls cellular lifespan through regulation of both the p16(Ink4a)/Rb and the Arf/p53 pathways Represses INK4a-ARF locus	Transcription factor	[44]	Normal human prostate epithelial cells
LPA(2)	inhibition	E2F induction	Phospholipid receptor	[45]	Mouse neuronal cells
Dbs	inhibition	E2F induction	Rho-specific guanine nucleotide exchange factor	[45]	Mouse neuronal cells
TBX2	inhibition	TBX2 represses the Cdkn2a (p19(ARF)) promoter	Transcription factor	[31]	Bmi1-/- MEFs
TBX3	inhibition	TBX-3 potently represses expression of both mouse p19(ARF) and human p14(ARF)	Transcription factor	[30]	Mouse neuronal cells
Topo1	promotion	DNA damage-ATM-p53	Nuclear enzyme regulating DNA structure Relaxes positively and negatively supercoiled DNA	[26]	Normal human cells
IGFBP7	promotion	MEK, ERK pathway In Brafv600E-mediated senescence, IGFBP7 inhibits BRAF-MEK-ERK signaling by inducing RKIP, which prevents BRAF from phosphorylating MEK	Ser/Thr protein kinase, oncogene Growth factor receptor	[25, 46]	Human primary fibroblasts, melanocytes
KLF4	promotion	p53 pathway Suppresses the expression of p53 by directly acting on its promoter Induces p21	Transcription factor	[47]	Conditionally immortalized MEFs co-expressing RASV12
SAHH	promotion	p53 pathway SAHH inactivation inhibits p53 transcriptional activity		[24b, 28, 48]	Primary human fibroblasts, Primary MEFs
CXCR2 (IL8RB)	promotion	p53 pathway CXCR2 knock-down alleviates both replicative and oncogene-induced senescence and diminishes the DNA-damage response.	Chemokine receptor	[49]	Primary human fibroblasts