Dynamics of p53 and NF-κB regulation in response to DNA damage and identification of target proteins suitable for therapeutic intervention

Table 1 Validation of the model on reported effects with functional p53

Inactivated Protein	DNA damage	Reported effects with functional p53	References	Model prediction
ATM	DSBs	· cell cycle arrest diminished	Lavin 2008	· cell cycle arrest blocked
		· cell cycle arrest diminished	Bolderson et al. 2009	· anti-apoptotic NF-κB (p50-p65-P) blocked
		· cell death enhanced		· anti-apoptotic NF-κB (p50-p65-P) blocked
				· apoptosis diminished
			Tofilon and Camphausen 2009	· apoptosis diminished
ATR	SSBs	· cell death enhanced	Flatten et al. 2005	· cell cycle arrest diminished
ATR	SSBs	· cell death enhanced	Wagner and Kaufmann 2010	· cell cycle arrest diminished
Chk1	SSBs	· cell cycle arrest diminished	Tse et al. 2007	· Cdc25A degradation diminished (degradation of Cdc25A leads to cell cycle arrest)
		· cell cycle arrest diminished	Ma et al. 2011
		· cell death enhanced	Ma et al. 2011	· p53 activation (causes apoptosis or cell cycle arrest) diminished
		· cell death enhanced	Garret and Collins 2011
Chk2	DSBs	cell death reduced	Morgan et al. 2010	· cell cycle arrest diminished
			Ma et al. 2011	· cell cycle arrest diminished
			Ma et al. 2011	· apoptosis diminished
			Garret and Collins 2011	· p53 activation (causes apoptosis or cell cycle arrest) diminished
TAK1	SSBs	· cell death enhanced	Martin et al. 2011	· cell cycle arrest diminished

ISSN: 1752-0509